Fibronectin Regulates the Dynamic Formation of Ovarian Cancer Multicellular Aggregates and the Expression of Integrin Receptors

Abstract

Objective: To investigate the regulatory role of fibronectin (FN) in the formation of multicellular aggregate (MCA)<br />in ovarian cancer SKOV3 and OVCAR-3 cells and integrin expression. Methods: The dynamic formation of MCA in<br />SKOV3 and OVCAR-3 was determined using the liquid overlay technique in the presence or absence of FN, anti-FN,<br />RGD peptide, control RGE. The expression of α3β1, α4β1 and α5β1 integrin in monolayer cells, MCA and FN-treated<br />MCA were determined by flow cytometry and quantitative RT-PCR. Results: OVCAR-3 and SKOV3 MCA were formed<br />on the 4th and 8th day and peaked on the 6th and 9th day, respectively. Treatment with different concentrations of FN,<br />LN, type IV collagen and control RGE peptide promoted MCA growth, which was mitigated by anti-FN and RGD<br />peptide. In comparison with monolayer cells, up-regulated α3β1, α4β1 and α5β1 expression were detected in MCA<br />while treatment with FN in both cells. Conclusions: OVCAR-3 and SKOV3 cells had varying dynamic formation of<br />MCA in our experimental system. FN enhanced MCA formation in both cells, which was associated with increased<br />expression of 3β1, α4β1 and α5β1 in the MCA. Therefore, FN and these integrins may be new therapeutic targets for<br />intervention of ovarian cancer metastasis.