Abstract
Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.
Highlights
Accepted: 26 March 2021Prostate cancer (PCa) is the most prevalent cancer among males in United States (US)with an estimated 248,530 cases in 2021 [1]
Abbreviations of messenger RNAs (mRNAs) and proteins are as follows—Transmembrane protein 256 (TM256), Late Endosomal/Lysosomal Adaptor, MAPK And MTOR Activator 1 (LAMTOR1),V-type proton ATPase 16 kDa proteolipid subunit (VATL), Adipogenesis regulatory factor (ADIRF), ETS Transcription Factor ERG (ERG), Prostate Cancer Antigen 3 (PCA3), Sterile alpha motif-pointed domain-containing Ets transcription factor (SPDEF), dimethylarginine dimethylaminohydrolase 1(DDAH1), Calsyntenin 1 (CLSTN1), Fatty acid synthase (FASN), Lactate Dehydrogenase A (LDHA), Annexin A2 (ANXA2), Clusterin (CLU), Enolase
1 (ENO1), Fibronectin 1 (FN1), Keratin 8 (KRT8), Laminin Subunit Alpha 5 (LAMA5), Nucleophosmin 1 (NPM1), Peroxiredoxin 1 (PRDX1), Transferrin Receptor (TFRC), Pyruvate kinase M2 (PKM2), PCa specific expression and EZH2-associated transcript (PCSEAT), SAP30L Antisense RNA 1 (Head To Head)(SAP30L-AS1), second chromosome locus associated with prostate-1 (SChLAP1), Kallikrein Related Peptidase 3 (KLK3), Androgen receptor splice variant 7 (AR-V7), Actinin Alpha 4 (ACTN4)
Summary
Prostate cancer (PCa) is the most prevalent cancer among males in United States (US). A majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, bone and lymph nodes. The precise mechanisms underlying PCa metastasis remain unclear which has led scientists to further explore this area. The precise mechanisms underlying PCa metastasis main unclear which has led scientists to further explore this area Another area of utmost importance is the identification of alternate prognostic and diagnostic biomarkers which will in better management of prostateand cancer and be of therapeutic relevance is thehelp identification of alternate prognostic diagnostic biomarkers which will help in [10].
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