The function of exosomes in prostate cancer
Ali Akbari barogi
,1,* Asiyeh jebelli
Prostate cancer is the second most common cancer in men. the prostate produces the fluid that carries sperm cells and is located below the bladder and in front of the rectum. nearly all prostate cancers begin in the gland cells that make prostate fluid. this is called an adenocarcinoma. early prostate cancer is generally asymptomatic while advanced prostate cancer can cause frequent urination, the feeling that the urethra is blocked and blood is observed in the semen. the prostate-specific antigen (psa) test is currently used to diagnose prostate cancer.
Exosomes are nano-sized membrane particles that are secreted by cells that transmit information from cell to cell. exosomes have been detected in nearly all kinds of body fluids, including blood, urine, saliva, amniotic fluid, cerebrospinal fluids, bile, ascites, tears, breast milk and semen. they have been found to play a vital role in many biological processes, including intercellular communication, immune function, development and differentiation of stem cells, neuronal function, cell signaling, tissue regeneration and viral replication. cancer derived exosomes can induce angiogenesis which plays a key role in the development of prostate cancer. prostate cancer exosomes have also been shown to further regulate the tumor microenvironment through activation of stromal cells to a disease-supporting myofibroblast-like phenotype and may be capable of modulating myeloid cells, thereby regulating immune and inflammatory responses within the tumor microenvironment.
Exosomes can shield cancer cells from therapeutic antibody attack, leading to the failure of antibody therapy. exosome contents play an important role in the drug resistance of prostate cancer cells. for example, mir-34 in prostate cancer cells and cell-derived exosomes targeted bcl-2 to regulate the response to docetaxel. exosomes could confer docetaxel-resistant cancer cells to docetaxel-sensitive cancer cells. a recent study identified 29 deregulated mirnas in exosomes from paclitaxel resistant prostate cancer cells, and these exosome-derived mirnas may contribute to prostate cancer chemoresistance. prostate cancer cell lines also produce typical exosomes, positive for prostate and cancer-associated antigens. the prostate cancer cell line lncap, for example, produces positive exosomal expression of psa and psma, prostate markers.
There is also clear positive exosomal expression of 5t4 antigene by lncap. in addition, prostate cancer cells derived exosomes can present tgf-β in vitro to transform fibroblasts to myofibroblasts via the activation of tgf-β/smad3 signaling. in the metastatic prostate cancer cell line pc-3, 266 proteins were identified with two or more peptide sequences. many of these proteins have previously been detected in exosomes, indicating that pc-3 vesicles have basic features in common with other types of exosomes at the protein level. in summary, there is sufficient evidence to suggest that prostate exosomes are capable of regulating cancer cell metabolism and tumor metastasis, and are capable of transferring drug resistance from one cell to another. such exosome-mediated effects, may impact tumor progression through direct or indirect mechanisms.
Prostate cancer, exosome, angiogenesis, chemoresistance