The role of exosome heterogeneity in epithelial ovarian cancer

Abstract

Ovarian cancer results in more deaths than any other gynecological malignancy, with a 5-year survival of only 30%. It is typically diagnosed after it has spread from the primary site to the secondary site. Exosomes are membrane-bound nanovesicles that play a critical role in tumor biology and metastasis by promoting intercellular communication. Tumor-associated exosome populations are widely acknowledged to be heterogenous, as various cell types and hallmark tumor microenvironment stressors impact exosome synthesis. Ovarian cancer cells metastasize using intraperitoneal fluids that are rich in exosomes, suggesting that these circulating exosomes assist detached cancer cells to maintain invasive phenotypes prior to secondary site invasion. Studies show that tumor-secreted exosomes direct organ-specific colonization by fusing exosome integrins with target cells in a tissue-specific fashion. Exosome signaling molecules (mRNA, miRNA, proteins) are encapsulated by cholesterol-rich membranes, and thus protects biomaterials from enzymatic degradation. Therefore, they represent an ideal system for studying the expression of sensitive proteins and RNA and for future drug delivery vehicles. Proteins and RNA exchanged through exosomes also influence the molecular and mechanical properties of ovarian cancer cells promoting adaptations that contribute to invasive and metastatic cell behavior. Tumor-derived exosomes also interact with stromal cells to alter their molecular profiles, thus promoting the development of a more malignant tumor microenvironment (TME), invasive cell behavior, and cancer progression. This review provides an overview on exosome structure and biogenesis and summarizes recent studies on ovarian cancer exosomes, exosome mediated interactions in the tumor microenvironment, and exosome heterogeneity.