Role of Exosomes in Prostate Cancer Metastasis

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.

FT-IR Spectral Signature of Sensitive and Multidrug-Resistant Osteosarcoma Cell-Derived Extracellular Nanovesicles

“…Indeed, breast cancer-derived EVs favor drug resistance by transferring pro-survival signals, reducing the intracellular accumulation of drugs, upregulating P-glycoprotein expression in sensitive cancer cells, and altering the epithelial-mesenchymal transition [33]. Similar mechanisms were also found in prostate cancer, where EVs contributed to docetaxel resistance [34], and ovarian cancer where EVs can deliver vascular-endothelial growth factor (VEGF) into endothelial cells causing resistance to anti-VEGF therapies [35]. EVs derived from the plasma of patients with acute myeloid leukemia (AML) confer idarubicin resistance in sensitive AML by inducing the expression of the drug efflux pumps MRD1 and MRP1 [36].…”

SNAP25 Is a Potential Prognostic Biomarker for Prostate Cancer

“…Moreover, results of cellular component analysis mainly focused on organelles involved in biosynthesis, cellular exosomes, and extracellular compartments. For example, mitochondrial dysfunction, abnormal organelle membrane potential [34] and exosome action [35] severely affect prostate cancer cells. In addition, KEGG pathway analysis revealed that xenobiotic metabolism, cytochrome P450 metabolism of xenobiotics, and chemical carcinogenesis were signi cantly associated with prostate cancer [36].…”

The Potential of Exosomes in Allergy Immunotherapy

“…Exosomes (40-160 nm) are of endosomal origin, which distinguishes them from ectosomes that bud from the surface of plasma membranes. Exosomes are surrounded by a bilayer lipid membrane composed of cholesterol, phosphatidylserines, and sphingolipids, which confer protection against proteases and RNases [22]. Exosome surface proteins include the classical exosome markers, the Tetraspanin proteins CD9, CD63, CD81, CD82, as well as adhesion molecules and the immune regulator molecules major histocompatibility complex (MHC) Class I and II [23].…”