Migration of breast epithelial cells on Laminin-5: differential role of integrins in normal and transformed cell types

We examined the role of Laminin-5 (Ln-5) an extracellular matrix component of breast gland basement membrane, in supporting migration of normal (HUMEC ), immortalized (MCF-10A), and malignant breast epithelial cells that exhib it different degrees of metastatic potential (MDA-MB-435>MDA-MB-231>MCF-7). HUMEC, MCF-10A, and MCF-7 cells all adhered to purified Ln-5 through the a lpha 3 beta 1 integrin receptor in adhesion assays. However, HUMEC and MCF- 10A cells remained statically adherent, while IZ MCF-7 cells migrated on Ln -5 in Transwell and colloidal gold displacement assays, Anti-alpha 3 integr in antibodies blocked migration of MCF-7 cells on Ln-5. MDA-MB-231 and MDA- MB-435 cells bound and migrated on Ln-5 through a beta 1 integrin receptor that is insensitive to antibodies that block the function of al. alpha 2, a lpha 3, alpha 4, alpha 5, alpha 6, and alpha V integrin subunits. Migration of all cell types tested was blocked by CM6, a monoclonal antibody directe d to a cell adhesion sits on the alpha 3 chain of Ln-5. Thus, Ln-5 may play an important role in regulating adhesion and migration in normal and trans formed breast epithelium. Our results indicate that the type of integrin ut ilized by breast cells to interact with Ln-5, as well as its functional sta te, may determine: whether cells will be statically adherent or migratory o n Ln-5.