The roles of integrins and extracellular matrix proteins in the insulin-like growth factor I-stimulated chemotaxis of human breast cancer cells

Abstract

The effects of insulin-like growth factor I (IGF-I) on the migration of two human breast cancer cell lines, MCF-7 and MDA-231, were examined using a modified Boyden chamber. 10 ng/ml was the optimal IGF-I concentration for stimulation of migration. The majority of IGF-I-stimulated migration in both cell types was due to chemotaxis. MCF-7 cells failed to migrate on membranes coated with gelatin or fibronectin and migrated only in small numbers on laminin. In contrast, when vitronectin- or type IV collagen-coated membranes were used, the MCF-7 cells migrated in large numbers specifically in response to IGF-I but not to 10% fetal calf serum, epidermal growth factor, fibroblast growth factor, or platelet derived growth factor-BB. An IGF-I receptorblocking antibody inhibited IGF-I-stimulated migration in both cell types. In addition, a blocking antibody to the αvβ5 integrin (a vitronectin receptor) inhibited migration of MCF-7 cells in response to IGF-I through vitronectin but not through type IV collagen. Similarly, blocking antibodies specific for α2 and βl integrins significantly inhibited migration of both cell types through type TV collagen-coated membranes but not through vitronectin-coated membranes. We conclude that: 1) IGF-I stimulates migration of these two cell types through the IGF-I receptor; 2) interaction of vitronectin with the αvβ5 integrin or collagen with the α2βl integrin is necessary for the complete IGF-I response in MCF-7 cells, and 3) because migration represents an in vitro model for metastatic spread, integrins, extracellular matrix proteins, and IGF-I may play coordinated roles in the metastasis of breast cancer in vivo.