Abstract
Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-β1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-β1, GRO-1, and IGF-1. Moreover, MAs upregulated α5β1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.
Highlights
Ovarian cancer, the most lethal gynecological malignancy [1], preferentially metastasizes into the peritoneal cavity [2]
The process of intraperitoneal dissemination of ovarian cancer is a highly complex and multistage phenomenon, and several elements are driven by malignant ascites (MAs), a peritoneal, inflammatory fluid that accumulates in excess in a large group of ovarian cancer patients [3]
Experiments using exogenous, recombinant forms of TGF-β1, HGF, GRO-1, and IGF-1 applied to respective cells at doses corresponding to their concentration in MAs provided clarification that both normal and cancer cells are sensitive to the identified mediators, which makes them responsible for the MAs-dependent increase in cancer cell adhesion (Figure 5)
Summary
The most lethal gynecological malignancy [1], preferentially metastasizes into the peritoneal cavity [2]. Very little is know about the effect of MAs on other critical aspects of ovarian cancer cell metastasis, Int.J.J.Mol. At the same time, very little is know about the effect of MAs on other critical aspects of ovarian cancer cell metastasis, Int.J.J.Mol Their adhesion to PMCs and peritoneal fibroblasts (PFBs). According to the current knowledge, both PMCs and PFBs actively stimulate cance cell adhesion [9,10]. This process islittle controlled reciprocal interactions between differen them to develop cancer-promoting [8].by. MAslittle on other critiabout theligands effect of MAs on other critical aspects of5β1 ovarian cancerinteracting metastasis, such as surface and receptors, of which integrins extracellula cal aspects of ovarian cancer cell metastasis, such α as their adhesion tocell.
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