Abstract
Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.
Highlights
Introduction314,000 new cases of ovarian cancer (OvCA) were diagnosed in 2020, with over 207,000 disease-related deaths
Worldwide, 314,000 new cases of ovarian cancer (OvCA) were diagnosed in 2020, with over 207,000 disease-related deaths
This review focuses on providing novel insights to understand how exosomes participate in OvCA progression through the peritoneum
Summary
314,000 new cases of ovarian cancer (OvCA) were diagnosed in 2020, with over 207,000 disease-related deaths. Malignant ascites is the result of leakiness of microvasculature, as well as obstruction of lymphatic vessels, and is frequently a sign of peritoneal affectation [22,23,24] Within this intraperitoneal fluidic microenvironment, tumor cells, mesothelial-derived CAFs, and infiltrating leukocytes produce a multitude of factors, including but not limited to cytokines, chemokines, and growth factors [15,23,25,26,27,28]. The content of exosomes shows specificity peritoneal affectation [22,23,24] Within this intraperitoneal fluidic microenvironment, to the cell of origin and depends, as well, on the functional state and regulated sorting tumor cells, mesothelial-derived CAFs, and infiltrating leukocytes produce a multitude of mechanisms of the cell, common components have been described for exosomes released by factors, including but not limited to cytokines, chemokines, and growth factors [15,23,25–. The new knowledge related to exosomes as potential biomarkers and therapeutic tools for peritoneal metastasis in OvCA will be briefly discussed
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