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.
The rationale and importance of folic acid supplementation during pregnancy for fetal congenital defect prevention are accepted worldwide. Moreover, a sufficient plasma concentration of folates can reduce the incidence of spontaneous abortions, and support the normal expansion of placental blood vessels, ensuring physiological placental blood flow, thus promoting appropriate fetal growth and development. Furthermore, there is emerging evidence that long-term supplementation with folic acid can effectively prevent preeclampsia. Preeclampsia is unique to the human species in complications during pregnancy, which contributes to maternal and perinatal mortality worldwide. In the pathogenesis of preeclampsia abnormal placental invasion, the excess of antiangiogenic factors and maternal–placental syndrome play a key role. Increased blood levels of homocysteine during pregnancy are associated with the risk of preeclampsia. Moreover, hyperhomocysteinemia has been proposed to be an independent risk factor for preeclampsia. Folate supplementation helps to decrease elevated levels of homocysteine; thus, the role of folic acid supplementation in pregnancy is even more important. Multiple reports suggest that folate administration decreases the level of serum homocysteine and, therefore, reduce the risk and severity of preeclampsia. However, the association between folic acid supplementation and the decreased risk of preeclampsia has been investigated with controversial conclusions. Currently, the optimal dose of folic acid that is effective for preeclampsia prevention remains uncertain. In this review, we aim to summarize the accumulated knowledge on the role of folic acid in the pathogenesis of preeclampsia, and the possible impact of folate supplementation on the decreased risk of preeclampsia.
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