Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms22084222
Keywords
cancer cell adhesion; malignant ascites; ovarian cancer; peritoneal metastases
Funding
- National Science Centre, Poland [2017/25/B/NZ3/00122, 2020/37/B/NZ5/00100]
- Social Health Insurance Project, Republic of Kazakhstan [SHIP2.3/CS-02]
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This study found that malignant ascites (MAs) promoted the adhesion of cancer cells to peritoneal cells more efficiently than benign ascites (BAs), possibly through the modulation of various growth factors affecting the interaction between cancer cells and normal cells.
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-beta 1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-beta 1, GRO-1, and IGF-1. Moreover, MAs upregulated alpha 5 beta 1 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.
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