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

摘要

Objective: To investigate the regulatory role of fibronectin (FN) in the formation of multicellular aggregate (MCA)in ovarian cancer SKOV3 and OVCAR-3 cells and integrin expression. Methods: The dynamic formation of MCA inSKOV3 and OVCAR-3 was determined using the liquid overlay technique in the presence or absence of FN, anti-FN,RGD peptide, control RGE. The expression of α3β1, α4β1 and α5β1 integrin in monolayer cells, MCA and FN-treatedMCA were determined by flow cytometry and quantitative RT-PCR. Results: OVCAR-3 and SKOV3 MCA were formedon the 4th and 8th day and peaked on the 6th and 9th day, respectively. Treatment with different concentrations of FN,LN, type IV collagen and control RGE peptide promoted MCA growth, which was mitigated by anti-FN and RGDpeptide. In comparison with monolayer cells, up-regulated α3β1, α4β1 and α5β1 expression were detected in MCAwhile treatment with FN in both cells. Conclusions: OVCAR-3 and SKOV3 cells had varying dynamic formation ofMCA in our experimental system. FN enhanced MCA formation in both cells, which was associated with increasedexpression of 3β1, α4β1 and α5β1 in the MCA. Therefore, FN and these integrins may be new therapeutic targets forintervention of ovarian cancer metastasis.