Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts

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.

Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

“…In addition to integrins, other factors present in the ascites can contribute to cell adhesion. A study by Uruski et al showed that in the presence of malignant ascites, A2780 and NIH:OVCAR-3 cells adhered more to peritoneal mesothelial cells and peritoneal fibroblasts compared to cells exposed to benign ascites [24]. Additionally, it was determined that A2780 cell adherence was dependent on transforming growth factor (TGF)-β1 and hepatocyte growth factor (HGF) while that of NIH:OVCAR-3 cells was dependent on TGF-β1, growth-related oncogene-1 (GRO-1), and insulin-like growth factor-1 (IGF-1) [24].…”

“…A study by Uruski et al showed that in the presence of malignant ascites, A2780 and NIH:OVCAR-3 cells adhered more to peritoneal mesothelial cells and peritoneal fibroblasts compared to cells exposed to benign ascites [24]. Additionally, it was determined that A2780 cell adherence was dependent on transforming growth factor (TGF)-β1 and hepatocyte growth factor (HGF) while that of NIH:OVCAR-3 cells was dependent on TGF-β1, growth-related oncogene-1 (GRO-1), and insulin-like growth factor-1 (IGF-1) [24]. Integrins were also examined in this study as well, and malignant ascites were found to upregulate α 5 β 1 integrin expression on peritoneal fibroblasts [24].…”

“…Additionally, it was determined that A2780 cell adherence was dependent on transforming growth factor (TGF)-β1 and hepatocyte growth factor (HGF) while that of NIH:OVCAR-3 cells was dependent on TGF-β1, growth-related oncogene-1 (GRO-1), and insulin-like growth factor-1 (IGF-1) [24]. Integrins were also examined in this study as well, and malignant ascites were found to upregulate α 5 β 1 integrin expression on peritoneal fibroblasts [24]. These findings further support the role of malignant ascites in integrin-dependent and -independent ovarian cancer adhesion and progression.…”

“…While substantial progress has been made in the areas of cellular, acellular, and biophysical contributions, much of this work has yet to be translated to improvements in clinical outcomes. Since the most common primary type of cancer associated with malignant ascites is ovarian cancer [5,6,[11][12][13][14][15][16][17][18][19][20][21][22][23][24], the focus of this review is the role of malignant ascites in ovarian cancer, specifically the contribution of ascites to advanced stage disease, modulation of the tumor microenvironment, remodeling of the extracellular matrix (ECM), and chemoresistance. In Section 2, major cellular and acellular components of ascites are introduced with a focus on the contribution of these factors to tumor growth, invasion, and metastasis.…”

High-Fat Diet-Induced Obese Effects of Adipocyte-Specific CXCR2 Conditional Knockout in the Peritoneal Tumor Microenvironment of Ovarian Cancer

“…This low survival rate is also attributable to the frequent and aggressive metastasis of OC throughout the peritoneal cavity, forming the secondary tumor foci and ascites [ 9 ]. The accumulation of malignant ascites provides growth factors, fatty acids, and chemokines to the OC cells, leading to a more aggressive and metastatic OC and a poor prognosis [ 10 , 11 ]. Chemokines are recognized as critical mediators in the tumor microenvironment and play a central role in regulating the inflammatory response, contributing to the progression and metastasis of OC [ 12 ].…”