Role of Integrins and IGFBPs in the IGF-1 Stimulated Migration of Human Breast Cancer Cells

摘要

We have previously shown that IGF-I stimulates chemotaxis of MCF-7 and MDA-23 1 human breast cancer cells. We now report that PDGF is a potent stimulant of migration. FGF is less effective, and EGF has no effects. The integrins that are present on 4 additional cell lines were identified. Antibodies that bind to the Beta 3 integrin inhibited migration in 3 of the 4 cell lines. Anti-alpha5 antibodies were also potent inhibitors. The combination of estradiol and IGF-I potently stimulated chemotaxis in MCF-7 cells, and the response to both hormones was greater than that to either hormone alone. Two IGF binding proteins were shown to alter the chemokinetic response of MDA-23 1 cells to IGF-I. IGFBP-3 inhibited the response to IGF-I. In contrast, IGFBP-5 enhanced the response to IGF-I, suggesting that different binding proteins have different effects.