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Health disparity of prostate cancer: 

Molecular insights into the role of exosomes  
 

Hamdy EA Ali1, Shaimaa A. Gad1, Gagan Deep2, Hamed I. Ali1, Zakaria Y. Abd Elmageed1*  
 

1Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M Health Sciences Center, Texas  
2Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 

 

*Corresponding Author: Zakaria Y. Abd Elmageed; e-mail: elmageed@tamhsc.edu 

 

ABSTRACT 

Prostate cancer (PCa) is the second leading cause of morbidity among older men in the States. The 

morbidity and mortality rates of PCa are twice as prevalent in African American (AA) than in Caucasian 

American (CA) men. Owing to the involvement of multiple factors contribute to such disparities, it 

remains unclear whether the high incidence and mortality rates of PCa among AA men are associated 

with genetic and epigenetic factors. The molecular mechanisms underlying these biological factors 

have yet to be fully elucidated. Exosomes are cell-derived extracellular bodies secreted by normal and 

tumor cells therefore promoting cell-cell communications. Exosomes are vesicular bodies that transfer 

different biological materials such as microRNAs, mRNAs, lipids, DNA and proteins to recipient cells. 

Our goal here is to illustrate the role of exosomes contributing to different biological activities, 

especially aggressive behavior of cancer cells and poor clinical outcomes of PCa in AA patients. There 

is a need to discover new biomarkers used in diagnosis and prognosis of PCa. It follows that a special 

focus on cancer disparities among AA men. This review indicates that more studies are needed to 

build on these recent findings for future understanding of the role of PCa-associated exosomes in 

promoting PCa aggressiveness in AA and other cancer disparities. Elucidating exosomal interactions in 

cancer and other chronic diseases should help to eliminate morbidity and mortality disparities among 

US minorities.  

 

KEYWORDS: Prostate cancer, Health disparity, Exosomes, microRNAs 

 

Citation: Ali HEA. et al. (2017). Health disparity of prostate cancer: Molecular insights into the role of 

exosomes. Cancer Health Disparities;1:e1-e13. DOI: 10.9777/chd.2017.10002 

 

 



 
 
 
 
 

 

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The incidence of prostate cancer remains high, 

biomarkers and molecular targets are an 

unmet need. Although the efforts in the field 

of biomedical research are advancing, more 

integrated research procedures and new 

strategies are still needed to promote early 

discovery, and hence reduce the burden while 

increasing the overall survival of cancer 

patients. Prostate cancer (PCa) is the second 

leading cause of death among older men in 

the United States (Jemal et al., 2008). After 

diagnosis, systemic therapies have been used 

as an option for managing the disease; 

however, chemotherapy is the ultimate 

solution, especially in castration-resistant PCa 

(CRPC) patients (Paller and Antonarakis, 2011). 

Although PCa is a multifactorial disease, 

androgens and their receptors (AR) represent 

the main driving forces for promoting PCa at 

all stages: initiation, progression and 

metastasis. Therefore, inhibition of AR and its 

downstream signaling pathways is the 

mainstream of current therapeutic targeting 

approaches. AR variant 7 (ARV7) is one of the 

most common AR variants that has a current 

clinical applications. ARV7 sequence contains 

the first three exons of the full length of AR 

sequence; exons 4-8 are replaced with a 

“cryptic exon” and, therefore, ARV7 lacks a 

ligand-binding domain. A recent emerging 

role of ARV7 in advanced PCa has been 

documented in PCa cells (Hu et al., 2009), 

animal models (Guo et al., 2009; Watson et al., 

2010) and CRPC patients (Del Re et al., 2017; 

Djusberg et al., 2017). The challenge in 

advanced stages of PCa is to develop new 

therapeutic agents and suppress androgen 

activity at its AR (wild form or its variants) 

and/or androgen metabolizing enzymes.  

The most common diagnostic tools for PCa 

are serum prostatic specific antigen (PSA), 

systematic prostate biopsies under ultrasound 

guidance and pathological staging with 

grading according to the Gleason score 

system (Heidenreich et al., 2014; Mottet et al., 

2017). Although PSA is still the gold standard 

utilized for detection of PCa, it is also elevated 

in men who have benign prostate 

hypertrophy, urinary tract infection, prostatitis, 

and after prostate surgeries and biopsies. 

Hence, the escalated level of PSA is not 

specific to PCa; this might lead to 

overdiagnosis followed by overtreatment 

accompanied with adding extra-cost on 

patients with low-risk of PCa (Lee et al., 2013). 

Other biomarkers have been developed to 

stratify patients according to their tumor stage, 

response to treatment, CRPC status, and 

metastasis. Current biomarkers, such as 

prostate cancer antigen 3 (PCA3), α-

methylacyl coenzyme A racemase (AMACR), 

TMPRSS2 (transmembrane serine protease 

isoform 2)-ERG (ETS transcription factor) gene 

fusion, and PTEN (phosphatase and tensin 

homolog) gene deletion, are clinically 

evaluated and some of them awaiting 

approvals. Accordingly, tremendous efforts 

have been directed towards the discovery of 

second-generation PCa biomarkers that can 

predict poor prognosis of the disease and can 

assist oncologists for proposing better 

treatment options for their patients. Owing to 

tumor heterogeneity, none of the current 

biomarkers is ideal to account for the wide 

variety of human samples, state of the disease 

and other clinical outcomes. As such, it is 

essential to develop new strategies for early 

detection and prognostication of PCa that may 

serve as surrogate endpoints for better 

evaluation of disease progression and effective 

treatment regimens thereby increasing 

patients’ survival.  



 
 
 
 
 

 

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Molecular mechanisms underlying health 

disparities of PCa have not been well 

determined. The mortality rate of PCa in 

African Americans (AA) is about twice that of 

Caucasian Americans (CA) or any other 

minorities (Hsing et al., 2000). Considering 

cancer disparity as a multifactorial event, it 

remains unclear whether the high incidence of 

mortality rate of PCa among AA men is 

promulgated principally by genetic, lifestyle, or 

socioeconomic-related factors. The molecular 

mechanisms underlying these discrepancies 

have yet to be fully elucidated. Levels of AME, 

growth factors, non-coding RNA and other 

genetic factors are higher in AA men than in 

other races (Hatcher et al., 2009; Khani et al., 

2014). Interestingly, the hormonal level of 

estrogen but not testosterone significantly 

differs between AA and CA men (Rohrmann et 

al., 2007). Our recent study substantiated 

higher circulating estrogen and selective 

expression of its receptor (ERβ) in PCa tissues 

of AA compared to CA men (Abd Elmageed et 

al., 2013). Presumably, another factor 

associated with disease aggressiveness in AA 

men is the overexpression of SPINK1 (serine 

peptidase inhibitor Kazal type-1) in tissues of 

AA men (Khani et al., 2014). Other genetic and 

epigenetic factors may involve in health 

disparities of PCa. For example, Chaudhary et 

al. (2016) reported that AA PCa cells exhibited 

reduced endogenous reactive oxygen species, 

mitochondrial membrane potential and less 

expression of heat shock proteins compared to 

CA PCa cells (Chaudhary et al., 2016). 

Intriguingly, the mitochondrial genome may 

contribute to the inherited racial disparities via 

the crosstalk between the mitochondria and 

the nucleus, which may overactivate signaling 

pathways in AA patients (Choudhury and 

Singh, 2017). Also, immunohistochemical 

studies on formalin-fixed paraffin-embedded 

tissues collected from 169 AA patients have 

demonstrated that, although PTEN and ERG 

expression are less frequent in AA patients, 

nonetheless, PTEN loss associated with poor 

prognosis of AA compared CA patients 

(Davenport, 2004). In a more recent study, the 

gene locus of RGS12 (regulator of G protein 

signaling 12) on chromosome 4p16.3 was not 

detected in AA men suggesting the tumor 

suppressive role of this gene in regulating 

cancer progression (Wang et al., 2017). In 

contrast, using three standard models of risk 

prediction in PCa, genotype and epigenetic 

data collected from 59,089 men of AA and CA 

origin exhibited insignificant difference 

between the two ethnicities suggesting high 

similarities in their genetics hallmarks (Gusev et 

al., 2016). 

microRNAs (miRs) are small non-coding 

regulatory RNAs that regulate gene expression 

at the post-transcriptional level. A growing 

body of evidence suggests that miRs are 

involved in the progression of many cancer 

types including PCa. Profiling of miRs has 

identified a specific set of miRs that can be 

utilized in PCa diagnosis and prognosis. The 

effect of miRs as epigenetic factors contributes 

disproportionately to PCa that has been 

recently studied. A group of scientists applied 

genomic-wide profiling for microRNAs (miRs)-

mRNA in 60 primary PCa compared to 16 

normal counterparts; they found that miR-

106b-25 cluster/MCM7 and miR-32/C9orf5 are 

highly expressed in PCa compared to controls 

(Ambs et al., 2008). Using integrative genomic 

approach, 10 specific miRs were identified 

along with their target genes, which were 

differentially expressed in to AA compared to 

CA men with PCa (Wang et al., 2015). In this 

regard, EGFR was the more likely signaling 

pathway used in cancer cells of AA origin. The 

https://www.ncbi.nlm.nih.gov/pubmed/?term=Chaudhary%20AK%5BAuthor%5D&cauthor=true&cauthor_uid=27115471


 
 
 
 
 

 

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same study also suggests that regulation of 

miR-mRNA crosstalk is the key step to control 

the oncogenic activities of miR-133a-MCL1, 

miR-513c-STAT1, miR-96-FOXO3A, miR-145-

ITPR2 and miR-34a-PPP2R2A in AA PCa tumor 

cells. miR-24 was reported to have a possible 

regulatory role in PCa progression based on 

the race. In this study, AA PCa cells MDA-PCa-

2b treated with 5-AZA-2'-deoxycytidine 

differentially restored miR-24 compared to CA 

PCa cells Du-145. Reconstitution of miR-24 in 

PCa cells reduced cells growth, induced cell 

death and decreased AR, ETV1, IGF1 and 

IGFB5 in AA cells (Hashimoto et al., 2017).  

 

The role of exosomes in PCa progression and 

metastasis  

Exosomes are cell-derived extracellular bodies 

(30-120 nm in size) secreted by normal and 

tumor cells to promote cell-cell 

communications. Exosomes acting as a 

delivery devices or shuttles for various 

biological molecules (microRNAs, mRNAs, 

lipids, DNA and proteins) to recipient cells 

(Mathivanan et al., 2012). Exosomes are 

detected in most of body fluids including 

blood, ascetic fluids, lymphatic fluids, urine, 

saliva, tears and milk. The molecular content of 

exosomes is dependent on their cell of origin. 

Therefore, the identification of tissue- or 

disease-specific exosomal proteins, miRNAs 

and mRNAs will enable the use of these 

vesicles as a source of new noninvasive 

biomarkers and serve as indicators in the 

diagnosis, prognosis and surveillance of a 

variety of diseases including cancer.  

The crosstalk between exosomes released 

from cancer cells as well as stromal cells in and 

around tumor niche, presumably along with 

other key players, is a critical factor for 

promoting metastasis. Carrying a message of 

exosomes from cells of origin  

‘donor’ and delivering it to the 

recipient/effector cells, depends on three main 

basic biological steps: biogenesis, release and 

internalization. During each step, there is a 

tight control of the quantity, biological 

contents and specificity of exosomes delivery 

to their target cells. The process of exosomal 

biogenesis and release is securely regulated by 

several factors inside the donor cells 

comprising endosomal sorting complex 

required for transport (ESCRT-o, -I, II, III) 

machinery, Syndecan-syntenin-ALIX, Rab 

proteins,  small integral membrane protein of 

the lysosome/late endosome (SIMPLE),  

phospholipase D, and sphingomyelinase 

(reviewed in (Hessvik and Llorente, 2017)). A 

growing body of research in exosomes 

suggests that their release by cancer and 

cancer-associated cells is a key-step for 

promoting PCa cell survival, growth, 

angiogenesis and suppression of immune 

system (Ge et al., 2012). Interestingly, 

collecting exosomes from highly metastatic 

melanoma cells promoted melanoma 

metastasis from the pre-metastatic site 

through reprogramming of bone marrow stem 

cells and silencing of Rab27A decreased 

exosomal production and reduced melanoma 

metastasis (Peinado et al., 2012). Our group 

demonstrated that exosomes are associated 

with PCa progression by transferring known 

and uncharacterized set(s) of miRs into 

recipient stem cells altering network of genes 

to transform non-malignant into PCa-like cells 

(Abd Elmageed et al., 2014). 

The tumor microenvironment contains a 

variety of cells such as fibroblasts, cancer-

associated fibroblasts (CAFs), endothelial cells, 

white cells, epithelial cells, and mesenchymal 



 
 
 
 
 

 

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stem cells as well as soluble growth factors, 

cytokines, chemokines, and exosomes (Ono et 

al., 2014). The different biological activities in 

which exosomes contribute to cell survival, cell 

proliferation, angiogenesis, 

immunomodulation and metastasis are 

depicted in Figure 1. Here, the role of 

exosomal cargoes in transferring different 

biologically active materials to exert specific 

biological effects on different cells in tumor 

niche (summarized in Table 1) are described. 

By activating TGF-β/SMAD3 signaling pathway, 

PCa-associated-exosomes can reprogram 

fibroblasts into CAFs, which is a critical step 

needed for cancer progression (Webber et al., 

2015). In the same vein, PCa-associated 

exosomes altered the 

adipogenic differentiation of mesenchymal 

stem cells towards CAFs, which gain 

proangiogenic activities by secreting VEGF-A, 

HGF and metalloproteinases (Chowdhury et 

al., 2015). Co-culturing of pancreatic cancer 

cells with primary pancreatic fibroblasts 

isolated from wild type C57 mice induced the 

transformation of fibroblasts to CAFs through 

exosomal miR-155-TP53INP1 axis (Pang et al., 

2015). Exosomes derived from CAFs have 

proven to transfer miRs to alter the tumor 

niche and promoting cell proliferation, 

invasion, epithelial-to-mesenchymal transition 

to develop chemoresistance in PCa cells (Au 

Yeung et al., 2016; Li et al., 2016a). Other 

research groups have reported that exosomes 

derived from different PCa cells and TRAMP 

mouse model are enriched with IGF-1R, SRC, 

FAK, CD9 and G-Protein-Coupled Receptor 

Kinases (GRK5 & 6) to support tumor 

progression and migration (DeRita et al., 2017; 

Soekmadji et al., 2016).  

 Exosomes released from PCa cells can directly 

or indireclty through circulation transfer their 

cargo contents (proteins, mRNA, microRNAs 

and lipids) into tumor microevironment (TME). 

TME contains fibroblasts, lymphocytes, 

macrophage, dentretic cells, extracellular 

matrix, and growth factors. This will change the 

signaling pathways in cancer and cancer-

associated cells to promote cell proliferation, 

survival, angiogenesis, metastasis and drug 

resisiatnce. These molecular events suggest 

that exosomes could be a determining factor 

contributing to health disparities among 

African American men. 

The role of exosomes in evasion of immune 

response in cancer disease is a growing area 

of research. Exosomes carry 

immunosuppressive molecules, tumor-

associated antigens, costimulatory molecules, 

major histocompatibility complex (MHC), and 

intraluminal cytokines (Whiteside, 2013, 2016). 

PCa-associated exosomes were found to 

express ligands of NKG2D (natural-killer group 

2, member D) and selectively suppress the 

expression of NKG2D on the surface of NK and 

CD8+ T cells- case leading to diminish the 

cytotoxic actions of these receptors (Lundholm 

et al., 2014). In a group of CRPC patients, the 

same investigators found a remarkable 

decrease of NKG2D expression on the surface 

of NK and CD8+ T cells regarding matched 

controls. Cancer-associated exosomes 

upregulate the suppressor activity of Treg and 

myeloid-derived suppressor to evade the 

immune response towards cancer cells (Xiang 

et al., 2009); this could occur by transferring of 

FasL, TGF-β, galectin-9 and HSP72 by 

exosomes into  recipient cells (Naito et al., 

2017).  

 

 



 
 
 
 
 

 

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Exosomes as non-invasive biomarkers in PCa 

In 2009, a group of researchers was able to 

detect the mRNA fusion gene TMRSS2: ERG 

and PCA-3 in the exosomes isolated from the 

urine of PCa patients. These findings suggest  

that circulating exosomes can act as a 

potential non-invasive biomarker by carrying 

in their cargoes of enriched mRNA compared 

to their donor cells (Nilsson et al., 2009). In 

American cohort, other scientists validated the 

accuracy of using TMPRSS2: ERG in urinary 

exosomes versus 21 PCa tissue specimens 

(Motamedinia et al., 2016). The detected 

TMPRSS2: ERG in urinary exosomes had 81% 

sensitivity, 80% specificity and 81% overall 

accuracy of the fused genes in exosomes 

collected from urine versus PCa tissues. This 

was followed by investigating the differential 

expression of TMPRSS2: ERG in large number 

of urine samples collected from 39 men with 

prostate biopsy negative, prostate biopsy 47 

biopsy positive, 37 men had radical 

prostatectomy, and 84 healthy men (44 age-

matched 40 young men). Data from ROC 

analyses showed that TMPRSS2: ERG, ERG, 

PCA3, BIRC5, and TMPRSS2 genes were able 

to segregate subjects with prostate biopsy 

positive from negative ones.  

 

 

 

 

Figure 1. Schematic representation showing suggested biological activities of exosomes in cell 

survival, cell proliferation, angiogenesis, immunomodulation and metastasis 

   



 
 
 
 
 

 

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Table 1. List of exosomes-associate cargoes transferred into recipient cells and used as biomarkers or 

have a biological impact  

Exosomes cargo Content  Effect/Role  Reference 

TGF-β Protein Transform fibroblast into cancer 

associated fibroblast 

(Webber et al., 2015) 

c-Src, IGF-IR, FAK Protein PCa progression (Del Re et al., 2017) 

CD9 Protein PCa progression (Soekmadji et al., 

2016) 

CD33, CD34, CD117, TGFβ1 Protein Decreased cytotoxic activity of NK 

towards cancer cells 

(Whiteside, 2013) 

FasL, PD-L1 

 

Protein Apoptosis of activated CD8+ Cells (Andreola et al., 2002; 

Kim et al., 2005) 

Ligands for NKG2D Protein  Has immunosuppressive effect (Lundholm et al., 2014) 

HSP72 Protein Has immunosuppressive effect (Chalmin et al., 2010) 

Galectin-9 Protein Apoptosis of T-Lymphocytes (Klibi et al., 2009) 

CD44 Protein Transform monocytes into tumor-

associated macrophage-like 

phenotypes 

(Baj-Krzyworzeka et 

al., 2007) 

DNA methyltransferase 1 

(DNMT1) 

Protein Cisplatin resistance in ovarian 

cancer cells 

(Cao et al., 2017) 

AR/ARV7 Protein Prostate cancer  (Read et al., 2017) 

miR-155 microRNA Transform fibroblast into cancer 

associated fibroblast by targeting 

TP53INP1  

(Pang et al., 2015) 

miR-17-3p, miR-21, miR-

106a, miR-146, miR-155, 

miR-191, miR-192, miR-

203, miR-205, miR-210, 

miR-12 and miR-214 

 

microRNA Tumor signature of lung 

adenocarcinoma 

(Rabinowits et al., 

2009) 

miR-21 microRNA Tumor progression in Esophageal 

squamous cell carcinoma 

 

(Tanaka et al., 2013) 

miR-551b, miR-96, mir-183, 

miR-182, miR-153, miR-

625, miR-141, miR-193b, 

miR-200c, miR-193a-3p, 

miR-205, miR-708, miR-365 

and miR-34 

 Tumor signature in PC-3 prostate 

cancer cell  

(Hessvik et al., 2012) 

miR-200c and miR-214 microRNA Tumor stage of ovarian cancer (Taylor and Gercel-



 
 
 
 
 

 

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Taylor, 2008) 

miR- miR-1290 and miR-

375 

microRNA prostate cancer prognosis (Huang et al., 2015) 

miR-16, miR-92a, miR- 103, 

miR-107, miR-97, miR-34b, 

miR-328, miR-485-3p, miR-

486-5p, miR-92b, miR-574-

3p, miR-636, miR-640, miR-

766 and miR-885-5p 

microRNA Prostate cancer (Stage 3&4) (Lodes et al., 2009) 

PCA3 Long 

non-

coding 

RNA 

Prostate cancer (Donovan et al., 2015) 

In plasma, exosomes were isolated from 67 

patients (39 PCa, 8 with recurrence and 20 

BPH) in addition to 16 healthy controls. In 

these exosomes, the expression of survivin was 

higher in PCa patients compared to BPH and 

health controls (Khan et al., 2012).  The acidic 

pH of tumor microenvironment increases the 

secretion of PSA- and CD81-expressing 

exosomes in PCa cells and as well as in 

peripheral blood of PCa patients 

corresponding to BPH and healthy controls 

(Logozzi et al., 2017). Proteomic analysis has 

shown that about 64 proteins were detected 

PC-3-associated exosomes and claudin 3 was 

the top expressed protein. CLDN3 level was 

assessed in plasma collected from 69 PCa in 

addition to BPH and control subjects. The 

expression of CLDN3 was specific to PCa 

patients versus other control groups (Worst et 

al., 2017). Interestingly, in vitro and preclinical 

studies aimed to investigate whether: 1) PCa-

associated exosomes express EGFR (Epidermal 

growth factor receptor) on their surface and 2) 

if it has any role in the aggressiveness of 

cancer cells. The study evidenced that the 

expression of EGFR in exosomes isolated from 

the conditioned media of PCa cell lines as well 

as LNCaP xenograft serum and patient blood 

(Kharmate et al., 2016). Nuclear translocation 

of EGFR in other cells was governed by PCa-

associated exosomes in an independent 

fashion of nuclear localization signal. In 

parallel, AR and its variant ARV7 have shown 

to be transferred through exosomes into the 

nucleus of AR-naïve PCa cells (Read et al., 

2017). It has been reported that exosomal 

gamma-glutamyltransferase activity is higher 

in the serum of PCa versus BPH patients. 

(Kawakami et al., 2017). 

RNA sequencing data demonstrated that miR-

1290, miR-1246, and miR-375 were top-listed 

miRs in exosomes isolated from the plasma 

procured from 21 CRCP patients. After their 

validation in 100 CRPC specimens, exosomes-

associated miR-1290 and miR-375 had a 

positive correlation with overall survival of PCa 

patients (Huang et al., 2015). The level of miR-

141 and miR-375 was assessed in exosomes 

collected from serum and data have shown 

that it was higher in 78 PCa compared to 28 

normal control subjects. There  was a positive 

correlation between miR-141 and miR-375 

with metastatic PCa (Bryant et al., 2012). 

Other miRs are dysregulated in PCa and can 

segregate in early versus late stages as well as 



 
 
 
 
 

 

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in localized versus metastatic status (Gallo et 

al., 2012; Li et al., 2016b; Lodes et al., 2009). 

 

Exosomes-based pathway in drug resistance of 

prostate cancer  

The development of CRPC is a current major 

concern in PCa management. Several 

mechanisms are proposed to understand how 

CRPC develops including: AR-independent 

tumor growth, conversion of estrogen to 

testosterone, activation of androgen 

metabolizing enzymes, intracrine activation of 

AR, and exosomes-based pathways. The 

multifactorial steps in developing resistance in 

PCa patients suggests the urgent need for 

adopting a new treatment strategy of 

targeting multiple signaling pathways 

contributing to CRPC and improving other 

methods of disease management. Treatment 

of CRPC patients with taxanes may lead to the 

development of resistance. The transfer of 

exosomal cargoes into different recipient cells 

could be one of CRPC mechanisms especially 

exosomes have shown to carry AR, ARV7, 

growth factors, mRNAs and miRNAs. Using a 

digital droplet PCR (ddPCR), a recent study 

suggested that plasma-derived exosomal 

mRNA of ARV7 is associated with resistance to 

hormonal therapy in patients with CRPC (Del 

Re et al., 2017). Along similar lines, exosomes 

were isolated from the blood of docetaxel-

resistant CRPC patients and was shown that 

their cargo contains MDR-1, MDR-

3 and PABP4 proteins (Endzelins et al., 2016). 

Kawakami  et al., performed proteomic 

analysis on exosomes isolated from taxane-

resistant PC-3 cells and, interestingly, integrin 

β4 and vinculin were upregulated (Kawakami 

et al., 2015). These findings present exosomal 

integrin β4, vinculin and MDR1 (Kato et al., 

2015) as new biomarkers in patients of taxane-

resistance.  In a recent study, pMet and miR-

130b were identified in exosomes isolated 

from sera of primary and metastatic PCa 

(Cannistraci et al., 2017). Both factors can 

significantly differentiate CRPC from early 

stages and can be used as non-invasive 

marker for active surveillance and therapy 

monitoring of CRPC patients. Li et al. 

investigated the potential networks of 

exosomes-associated miRNAs derived from 

chemoresistant PCa cells with their known 

target genes (Li et al., 2016a). They identified 

29 dysregulated miRNAs, in exosome isolated 

from paclitaxel-resistance PCa cells. The link 

between miRNAs and their target genes 

suggests that miR-3176, miR-141-3p, miR-

5004-5p, miR-16-5p, miR-3915, miR-488-3p, 

miR-23c, miR-3673 and miR-3654 are 

potential targets to AR and PTEN while miR-

32-5, miR-141-3p, miR-606, miR-381 and miR-

429 are targets to TCF4. In another study 

conducted on neuorblastoma cells, exosomes-

associated miR-21 and miR-155 mediate the 

crosstalk between neuroblastoma cells and 

monocytes in cisplatin resistance cells, possibly, 

through miR-21/TLR8-NF-кB and miR-

155/TERF1 signaling pathways (Challagundla 

et al., 2015). 

 

Concluding remarks 

The role of exosomes is emerging as an 

interesting component in cancer biology but 

their contribution to cancer disparities and 

drug resistance remains unclear. Increasing 

evidence points towards eminent role of 

exosomal cargoes in transferring cellular 

messages between cancer cells and their 

tumor niche. The presence of exosomal 

protein receptors on the surface of PCa-

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associated exosomes may explain, in part, the 

reasons of PCa disparities among AA men 

regarding CA men and other minorities. This 

review justifies the need for more studies to 

build on these recent findings for future 

understanding of the role of PCa-associated 

exosomes in promoting health 

disproportionate in PCa and other cancer 

disparities. Adopting such exosomal findings in 

cancer and other chronic diseases might help 

to eliminate morbidity and mortality disparities 

among different minorities. Future studies 

need to address these questions to fasciltate 

the development of new generations of 

therapeutic agents to target tumor exosomes. 

In parallel, exosomes standardization for their 

detection and evaluation as well as 

understanding their biogenesis, release and 

uptake are of paramount importance. With a 

growing accessibility to these biological 

information, new specific and less toxic drugs 

will be discovered.     

 

Acknowledgements 

The authors would like to thank Dr. David 

Potter, Ph.D., FARVO, for helpful discussions 

and carefully reading the manuscript. The 

present study was supported by grant from 

the NIH/NCI R21CA194750 (Z.Y.A). 

 

Conflict of interest statement 

The authors declare that there is no conflict of 

interest to report it. The funders had no role in 

study design, writing of the manuscript and 

decision to publish.    

 

Authors’ contributions 

Conception and design of the study: ZYA; data 

collection and preparation: HEAA and SAG; 

writing the manuscript: HEAA, HIA, SAG, GD 

and ZYA; reviewing the final version of the 

manuscript: GA, HIA and ZYA. 

 

REFERENCES 

Abd Elmageed, Z.Y., Moroz, K., Srivastav, S.K., Fang, Z., 

Crawford, B.E., Moparty, K., Thomas, R., and Abdel-

Mageed, A.B. (2013). High circulating estrogens and 

selective expression of ERbeta in prostate tumors of 

Americans: implications for racial disparity of prostate 

cancer. Carcinogenesis 34, 2017-2023. 

Abd Elmageed, Z.Y., Yang, Y., Thomas, R., Ranjan, M., Mondal, 

D., Moroz, K., Fang, Z., Rezk, B.M., Moparty, K., Sikka, S.C., 

et al. (2014). Neoplastic reprogramming of patient-derived 

adipose stem cells by prostate cancer cell-associated 

exosomes. Stem Cells 32, 983-997. 

Ambs, S., Prueitt, R.L., Yi, M., Hudson, R.S., Howe, T.M., Petrocca, 

F., Wallace, T.A., Liu, C.G., Volinia, S., Calin, G.A., et al. 

(2008). Genomic profiling of microRNA and messenger 

RNA reveals deregulated microRNA expression in prostate 

cancer. Cancer Res 68, 6162-6170. 

Andreola, G., Rivoltini, L., Castelli, C., Huber, V., Perego, P., 

Deho, P., Squarcina, P., Accornero, P., Lozupone, F., Lugini, 

L., et al. (2002). Induction of lymphocyte apoptosis by 

tumor cell secretion of FasL-bearing microvesicles. J Exp 

Med 195, 1303-1316. 

Au Yeung, C.L., Co, N.N., Tsuruga, T., Yeung, T.L., Kwan, S.Y., 

Leung, C.S., Li, Y., Lu, E.S., Kwan, K., Wong, K.K., et al. 

(2016). Exosomal transfer of stroma-derived miR21 confers 

paclitaxel resistance in ovarian cancer cells through 

targeting APAF1. Nat Commun 7, 11150. 

Baj-Krzyworzeka, M., Szatanek, R., Weglarczyk, K., Baran, J., and 

Zembala, M. (2007). Tumour-derived microvesicles 

modulate biological activity of human monocytes. Immunol 

Lett 113, 76-82. 

Bryant, R.J., Pawlowski, T., Catto, J.W., Marsden, G., Vessella, R.L., 

Rhees, B., Kuslich, C., Visakorpi, T., and Hamdy, F.C. (2012). 

Changes in circulating microRNA levels associated with 

prostate cancer. Br J Cancer 106, 768-774. 

Cannistraci, A., Federici, G., Addario, A., Di Pace, A.L., Grassi, L., 

Muto, G., Collura, D., Signore, M., De Salvo, L., Sentinelli, S., 

et al. (2017). C-Met/miR-130b axis as novel mechanism 

and biomarker for castration resistance state acquisition. 

Oncogene 36, 3718-3728. 

Cao, Y.L., Zhuang, T., Xing, B.H., Li, N., and Li, Q. (2017). 

Exosomal DNMT1 mediates cisplatin resistance in ovarian 

cancer. Cell Biochem Funct. 

Challagundla, K.B., Wise, P.M., Neviani, P., Chava, H., Murtadha, 

M., Xu, T., Kennedy, R., Ivan, C., Zhang, X., Vannini, I., et al. 

(2015). Exosome-mediated transfer of microRNAs within 

the tumor microenvironment and neuroblastoma 

resistance to chemotherapy. J Natl Cancer Inst 107. 

Chalmin, F., Ladoire, S., Mignot, G., Vincent, J., Bruchard, M., 

Remy-Martin, J.P., Boireau, W., Rouleau, A., Simon, B., 

Lanneau, D., et al. (2010). Membrane-associated Hsp72 



 
 
 
 
 

 

www.eopenaccess.com/index.php/chd                           e11                                         Cancer Health Disparities 

REVIEW 

from tumor-derived exosomes mediates STAT3-dependent 

immunosuppressive function of mouse and human 

myeloid-derived suppressor cells. J Clin Invest 120, 457-

471. 

Chaudhary, A.K., Bhat, T.A., Kumar, S., Kumar, A., Kumar, R., 

Underwood, W., Koochekpour, S., Shourideh, M., Yadav, 

N., Dhar, S., et al. (2016). Mitochondrial dysfunction-

mediated apoptosis resistance associates with defective 

heat shock protein response in African-American men with 

prostate cancer. Br J Cancer 114, 1090-1100. 

Choudhury, A.R., and Singh, K.K. (2017). Mitochondrial 

determinants of cancer health disparities. Semin Cancer 

Biol. 

Chowdhury, R., Webber, J.P., Gurney, M., Mason, M.D., Tabi, Z., 

and Clayton, A. (2015). Cancer exosomes trigger 

mesenchymal stem cell differentiation into pro-angiogenic 

and pro-invasive myofibroblasts. Oncotarget 6, 715-731. 

Davenport, R.J. (2004). Culture clash.A growing body of research 

suggests that yeast have programmed death pathways, yet 

many researchers are skeptical. Recent studies provide 

some of the first experimental evidence for why a single-

celled organism would commit suicide. Sci Aging 

Knowledge Environ 2004, ns9. 

Del Re, M., Biasco, E., Crucitta, S., Derosa, L., Rofi, E., Orlandini, 

C., Miccoli, M., Galli, L., Falcone, A., Jenster, G.W., et al. 

(2017). The Detection of Androgen Receptor Splice Variant 

7 in Plasma-derived Exosomal RNA Strongly Predicts 

Resistance to Hormonal Therapy in Metastatic Prostate 

Cancer Patients. Eur Urol 71, 680-687. 

DeRita, R.M., Zerlanko, B., Singh, A., Lu, H., Iozzo, R.V., Benovic, 

J.L., and Languino, L.R. (2017). c-Src, Insulin-Like Growth 

Factor I Receptor, G-Protein-Coupled Receptor Kinases 

and Focal Adhesion Kinase are Enriched Into Prostate 

Cancer Cell Exosomes. J Cell Biochem 118, 66-73. 

Djusberg, E., Jernberg, E., Thysell, E., Golovleva, I., Lundberg, P., 

Crnalic, S., Widmark, A., Bergh, A., Brattsand, M., and 

Wikstrom, P. (2017). High levels of the AR-V7 Splice Variant 

and Co-Amplification of the Golgi Protein Coding YIPF6 in 

AR Amplified Prostate Cancer Bone Metastases. Prostate 

77, 625-638. 

Donovan, M.J., Noerholm, M., Bentink, S., Belzer, S., Skog, J., 

O'Neill, V., Cochran, J.S., and Brown, G.A. (2015). A 

molecular signature of PCA3 and ERG exosomal RNA from 

non-DRE urine is predictive of initial prostate biopsy result. 

Prostate Cancer Prostatic Dis 18, 370-375. 

Endzelins, E., Melne, V., Kalnina, Z., Lietuvietis, V., Riekstina, U., 

Llorente, A., and Line, A. (2016). Diagnostic, prognostic and 

predictive value of cell-free miRNAs in prostate cancer: a 

systematic review. Mol Cancer 15, 41. 

Gallo, A., Tandon, M., Alevizos, I., and Illei, G.G. (2012). The 

majority of microRNAs detectable in serum and saliva is 

concentrated in exosomes. PLoS One 7, e30679. 

Ge, R., Tan, E., Sharghi-Namini, S., and Asada, H.H. (2012). 

Exosomes in Cancer Microenvironment and Beyond: have 

we Overlooked these Extracellular Messengers? Cancer 

Microenviron 5, 323-332. 

Guo, Z., Yang, X., Sun, F., Jiang, R., Linn, D.E., Chen, H., Chen, H., 

Kong, X., Melamed, J., Tepper, C.G., et al. (2009). A novel 

androgen receptor splice variant is up-regulated during 

prostate cancer progression and promotes androgen 

depletion-resistant growth. Cancer Res 69, 2305-2313. 

Gusev, A., Shi, H., Kichaev, G., Pomerantz, M., Li, F., Long, H.W., 

Ingles, S.A., Kittles, R.A., Strom, S.S., Rybicki, B.A., et al. 

(2016). Atlas of prostate cancer heritability in European and 

African-American men pinpoints tissue-specific regulation. 

Nat Commun 7, 10979. 

Hashimoto, Y., Shiina, M., Kato, T., Yamamura, S., Tanaka, Y., 

Majid, S., Saini, S., Shahryari, V., Kulkarni, P., Dasgupta, P., 

et al. (2017). The role of miR-24 as a race related genetic 

factor in prostate cancer. Oncotarget 8, 16581-16593. 

Hatcher, D., Daniels, G., Osman, I., and Lee, P. (2009). Molecular 

mechanisms involving prostate cancer racial disparity. Am J 

Transl Res 1, 235-248. 

Heidenreich, A., Bastian, P.J., Bellmunt, J., Bolla, M., Joniau, S., 

van der Kwast, T., Mason, M., Matveev, V., Wiegel, T., 

Zattoni, F., et al. (2014). EAU guidelines on prostate cancer. 

part 1: screening, diagnosis, and local treatment with 

curative intent-update 2013. Eur Urol 65, 124-137. 

Hessvik, N.P., and Llorente, A. (2017). Current knowledge on 

exosome biogenesis and release. Cell Mol Life Sci. 

Hessvik, N.P., Phuyal, S., Brech, A., Sandvig, K., and Llorente, A. 

(2012). Profiling of microRNAs in exosomes released from 

PC-3 prostate cancer cells. Biochim Biophys Acta 1819, 

1154-1163. 

Hsing, A.W., Tsao, L., and Devesa, S.S. (2000). International 

trends and patterns of prostate cancer incidence and 

mortality. International journal of cancer Journal 

international du cancer 85, 60-67. 

Hu, R., Dunn, T.A., Wei, S., Isharwal, S., Veltri, R.W., Humphreys, 

E., Han, M., Partin, A.W., Vessella, R.L., Isaacs, W.B., et al. 

(2009). Ligand-independent androgen receptor variants 

derived from splicing of cryptic exons signify hormone-

refractory prostate cancer. Cancer Res 69, 16-22. 

Huang, X., Yuan, T., Liang, M., Du, M., Xia, S., Dittmar, R., Wang, 

D., See, W., Costello, B.A., Quevedo, F., et al. (2015). 

Exosomal miR-1290 and miR-375 as prognostic markers in 

castration-resistant prostate cancer. Eur Urol 67, 33-41. 

Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., and 

Thun, M.J. (2008). Cancer statistics, 2008. CA Cancer J Clin 

58, 71-96. 

Kato, T., Mizutani, K., Kameyama, K., Kawakami, K., Fujita, Y., 

Nakane, K., Kanimoto, Y., Ehara, H., Ito, H., Seishima, M., et 

al. (2015). Serum exosomal P-glycoprotein is a potential 

marker to diagnose docetaxel resistance and select a 

taxoid for patients with prostate cancer. Urol Oncol 33, 385 

e315-320. 

Kawakami, K., Fujita, Y., Kato, T., Mizutani, K., Kameyama, K., 

Tsumoto, H., Miura, Y., Deguchi, T., and Ito, M. (2015). 

Integrin beta4 and vinculin contained in exosomes are 

potential markers for progression of prostate cancer 

associated with taxane-resistance. Int J Oncol 47, 384-390. 

Kawakami, K., Fujita, Y., Matsuda, Y., Arai, T., Horie, K., 

Kameyama, K., Kato, T., Masunaga, K., Kasuya, Y., Tanaka, 



 
 
 
 
 

 

www.eopenaccess.com/index.php/chd                           e12                                         Cancer Health Disparities 

REVIEW 

M., et al. (2017). Gamma-glutamyltransferase activity in 

exosomes as a potential marker for prostate cancer. BMC 

Cancer 17, 316. 

Khan, S., Jutzy, J.M., Valenzuela, M.M., Turay, D., Aspe, J.R., 

Ashok, A., Mirshahidi, S., Mercola, D., Lilly, M.B., and Wall, 

N.R. (2012). Plasma-derived exosomal survivin, a plausible 

biomarker for early detection of prostate cancer. PLoS One 

7, e46737. 

Khani, F., Mosquera, J.M., Park, K., Blattner, M., O'Reilly, C., 

MacDonald, T.Y., Chen, Z., Srivastava, A., Tewari, A.K., 

Barbieri, C.E., et al. (2014). Evidence for molecular 

differences in prostate cancer between African American 

and Caucasian men. Clin Cancer Res 20, 4925-4934. 

Kharmate, G., Hosseini-Beheshti, E., Caradec, J., Chin, M.Y., and 

Tomlinson Guns, E.S. (2016). Epidermal Growth Factor 

Receptor in Prostate Cancer Derived Exosomes. PLoS One 

11, e0154967. 

Kim, J.W., Wieckowski, E., Taylor, D.D., Reichert, T.E., Watkins, S., 

and Whiteside, T.L. (2005). Fas ligand-positive 

membranous vesicles isolated from sera of patients with 

oral cancer induce apoptosis of activated T lymphocytes. 

Clin Cancer Res 11, 1010-1020. 

Klibi, J., Niki, T., Riedel, A., Pioche-Durieu, C., Souquere, S., 

Rubinstein, E., Le Moulec, S., Guigay, J., Hirashima, M., 

Guemira, F., et al. (2009). Blood diffusion and Th1-

suppressive effects of galectin-9-containing exosomes 

released by Epstein-Barr virus-infected nasopharyngeal 

carcinoma cells. Blood 113, 1957-1966. 

Lee, Y.J., Park, J.E., Jeon, B.R., Lee, S.M., Kim, S.Y., and Lee, Y.K. 

(2013). Is prostate-specific antigen effective for population 

screening of prostate cancer? A systematic review. Ann Lab 

Med 33, 233-241. 

Li, J., Yang, X., Guan, H., Mizokami, A., Keller, E.T., Xu, X., Liu, X., 

Tan, J., Hu, L., Lu, Y., et al. (2016a). Exosome-derived 

microRNAs contribute to prostate cancer chemoresistance. 

Int J Oncol 49, 838-846. 

Li, Z., Ma, Y.Y., Wang, J., Zeng, X.F., Li, R., Kang, W., and Hao, 

X.K. (2016b). Exosomal microRNA-141 is upregulated in 

the serum of prostate cancer patients. Onco Targets Ther 

9, 139-148. 

Lodes, M.J., Caraballo, M., Suciu, D., Munro, S., Kumar, A., and 

Anderson, B. (2009). Detection of cancer with serum 

miRNAs on an oligonucleotide microarray. PLoS One 4, 

e6229. 

Logozzi, M., Angelini, D.F., Iessi, E., Mizzoni, D., Di Raimo, R., 

Federici, C., Lugini, L., Borsellino, G., Gentilucci, A., Pierella, 

F., et al. (2017). Increased PSA expression on prostate 

cancer exosomes in in vitro condition and in cancer 

patients. Cancer Lett 403, 318-329. 

Lundholm, M., Schroder, M., Nagaeva, O., Baranov, V., Widmark, 

A., Mincheva-Nilsson, L., and Wikstrom, P. (2014). Prostate 

tumor-derived exosomes down-regulate NKG2D 

expression on natural killer cells and CD8+ T cells: 

mechanism of immune evasion. PLoS One 9, e108925. 

Mathivanan, S., Fahner, C.J., Reid, G.E., and Simpson, R.J. (2012). 

ExoCarta 2012: database of exosomal proteins, RNA and 

lipids. Nucleic Acids Res 40, D1241-1244. 

Motamedinia, P., Scott, A.N., Bate, K.L., Sadeghi, N., Salazar, G., 

Shapiro, E., Ahn, J., Lipsky, M., Lin, J., Hruby, G.W., et al. 

(2016). Urine Exosomes for Non-Invasive Assessment of 

Gene Expression and Mutations of Prostate Cancer. PLoS 

One 11, e0154507. 

Mottet, N., Bellmunt, J., Bolla, M., Briers, E., Cumberbatch, M.G., 

De Santis, M., Fossati, N., Gross, T., Henry, A.M., Joniau, S., 

et al. (2017). EAU-ESTRO-SIOG Guidelines on Prostate 

Cancer. Part 1: Screening, Diagnosis, and Local Treatment 

with Curative Intent. Eur Urol 71, 618-629. 

Naito, Y., Yoshioka, Y., Yamamoto, Y., and Ochiya, T. (2017). 

How cancer cells dictate their microenvironment: present 

roles of extracellular vesicles. Cell Mol Life Sci 74, 697-713. 

Nilsson, J., Skog, J., Nordstrand, A., Baranov, V., Mincheva-

Nilsson, L., Breakefield, X.O., and Widmark, A. (2009). 

Prostate cancer-derived urine exosomes: a novel approach 

to biomarkers for prostate cancer. Br J Cancer 100, 1603-

1607. 

Ono, M., Kosaka, N., Tominaga, N., Yoshioka, Y., Takeshita, F., 

Takahashi, R.U., Yoshida, M., Tsuda, H., Tamura, K., and 

Ochiya, T. (2014). Exosomes from bone marrow 

mesenchymal stem cells contain a microRNA that 

promotes dormancy in metastatic breast cancer cells. Sci 

Signal 7, ra63. 

Paller, C.J., and Antonarakis, E.S. (2011). Cabazitaxel: a novel 

second-line treatment for metastatic castration-resistant 

prostate cancer. Drug Des Devel Ther 5, 117-124. 

Pang, W., Su, J., Wang, Y., Feng, H., Dai, X., Yuan, Y., Chen, X., 

and Yao, W. (2015). Pancreatic cancer-secreted miR-155 

implicates in the conversion from normal fibroblasts to 

cancer-associated fibroblasts. Cancer Sci 106, 1362-1369. 

Peinado, H., Aleckovic, M., Lavotshkin, S., Matei, I., Costa-Silva, 

B., Moreno-Bueno, G., Hergueta-Redondo, M., Williams, C., 

Garcia-Santos, G., Ghajar, C., et al. (2012). Melanoma 

exosomes educate bone marrow progenitor cells toward a 

pro-metastatic phenotype through MET. Nat Med 18, 883-

891. 

Rabinowits, G., Gercel-Taylor, C., Day, J.M., Taylor, D.D., and 

Kloecker, G.H. (2009). Exosomal microRNA: a diagnostic 

marker for lung cancer. Clin Lung Cancer 10, 42-46. 

Read, J., Ingram, A., Al Saleh, H.A., Platko, K., Gabriel, K., Kapoor, 

A., Pinthus, J., Majeed, F., Qureshi, T., and Al-Nedawi, K. 

(2017). Nuclear transportation of exogenous epidermal 

growth factor receptor and androgen receptor via 

extracellular vesicles. Eur J Cancer 70, 62-74. 

Rohrmann, S., Nelson, W.G., Rifai, N., Brown, T.R., Dobs, A., 

Kanarek, N., Yager, J.D., and Platz, E.A. (2007). Serum 

estrogen, but not testosterone, levels differ between black 

and white men in a nationally representative sample of 

Americans. J Clin Endocrinol Metab 92, 2519-2525. 

Soekmadji, C., Riches, J.D., Russell, P.J., Ruelcke, J.E., McPherson, 

S., Wang, C., Hovens, C.M., Corcoran, N.M., The Australian 

Prostate Cancer Collaboration, B., Hill, M.M., et al. (2016). 

Modulation of paracrine signaling by CD9 positive small 

extracellular vesicles mediates cellular growth of androgen 

deprived prostate cancer. Oncotarget. 



 
 
 
 
 

 

www.eopenaccess.com/index.php/chd                           e13                                         Cancer Health Disparities 

REVIEW 

Tanaka, Y., Kamohara, H., Kinoshita, K., Kurashige, J., Ishimoto, 

T., Iwatsuki, M., Watanabe, M., and Baba, H. (2013). Clinical 

impact of serum exosomal microRNA-21 as a clinical 

biomarker in human esophageal squamous cell carcinoma. 

Cancer 119, 1159-1167. 

Taylor, D.D., and Gercel-Taylor, C. (2008). MicroRNA signatures 

of tumor-derived exosomes as diagnostic biomarkers of 

ovarian cancer. Gynecol Oncol 110, 13-21. 

Wang, B.D., Ceniccola, K., Yang, Q., Andrawis, R., Patel, V., Ji, Y., 

Rhim, J., Olender, J., Popratiloff, A., Latham, P., et al. (2015). 

Identification and Functional Validation of Reciprocal 

microRNA-mRNA Pairings in African American Prostate 

Cancer Disparities. Clin Cancer Res 21, 4970-4984. 

Wang, Y., Wang, J., Zhang, L., Karatas, O.F., Shao, L., Zhang, Y., 

Castro, P., Creighton, C.J., and Ittmann, M. (2017). RGS12 Is 

a Novel Tumor-Suppressor Gene in African American 

Prostate Cancer That Represses AKT and MNX1 Expression. 

Cancer Res. 

Watson, P.A., Chen, Y.F., Balbas, M.D., Wongvipat, J., Socci, N.D., 

Viale, A., Kim, K., and Sawyers, C.L. (2010). Constitutively 

active androgen receptor splice variants expressed in 

castration-resistant prostate cancer require full-length 

androgen receptor. Proc Natl Acad Sci U S A 107, 16759-

16765. 

Webber, J.P., Spary, L.K., Sanders, A.J., Chowdhury, R., Jiang, 

W.G., Steadman, R., Wymant, J., Jones, A.T., Kynaston, H., 

Mason, M.D., et al. (2015). Differentiation of tumour-

promoting stromal myofibroblasts by cancer exosomes. 

Oncogene 34, 290-302. 

Whiteside, T.L. (2013). Immune modulation of T-cell and NK 

(natural killer) cell activities by TEXs (tumour-derived 

exosomes). Biochem Soc Trans 41, 245-251. 

Whiteside, T.L. (2016). Tumor-Derived Exosomes and Their Role 

in Tumor-Induced Immune Suppression. Vaccines (Basel) 4. 

Worst, T.S., von Hardenberg, J., Gross, J.C., Erben, P., Schnolzer, 

M., Hausser, I., Bugert, P., Michel, M.S., and Boutros, M. 

(2017). Database-augmented Mass Spectrometry Analysis 

of Exosomes Identifies Claudin 3 as a Putative Prostate 

Cancer Biomarker. Mol Cell Proteomics 16, 998-1008. 

Xiang, X., Poliakov, A., Liu, C., Liu, Y., Deng, Z.B., Wang, J., 

Cheng, Z., Shah, S.V., Wang, G.J., Zhang, L., et al. (2009). 

Induction of myeloid-derived suppressor cells by tumor 

exosomes. Int J Cancer 124, 2621-2633. 

 

 


