Procancerogenic activity of senescent cells: A case of the peritoneal mesothelium.

Human peritoneal mesothelial cells belong to a narrow group of somatic cells in which both the triggers and the mechanisms of senescence have already been well defined. Importantly, senescent mesothelial cells have been found in the peritoneal cavity in vivo. From a clinical point of view, peritoneal mesothelial cells have been recognized as playing a critical role in the intraperitoneal development of tumor metastases. The pro-cancerogenic behavior of mesothelial cells is even more pronounced when the cells exhaust their proliferative capacity and become senescent. In this review, we summarize the current state of art regarding the contribution of peritoneal mesothelial cells in the progression of ovarian, colorectal, and pancreatic carcinomas, with particular attention paid to the cancer-promoting activity of their senescent counterparts. Moreover, we delineate the mechanisms, mediators, and signaling pathways that are engaged by the senescent mesothelial cells to support such vital elements of cancer progression as adhesion, proliferation, migration, invasion, epithelial-mesenchymal transition, and angiogenesis. Finally, we discuss the experimental evidence regarding both natural and synthetic compounds that may either prevent or restrict cancer development by delaying senescence of mesothelial cells.