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 exhibit 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 alpha3beta1 integrin receptor in adhesion assays. However, HUMEC and MCF-10A cells remained statically adherent, while MCF-7 cells migrated on Ln-5 in Transwell and colloidal gold displacement assays. Anti-alpha3 integrin 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 beta1 integrin receptor that is insensitive to antibodies that block the function of alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, and alphaV integrin subunits. Migration of all cell types tested was blocked by CM6, a monoclonal antibody directed to a cell adhesion site on the alpha3 chain of Ln-5. Thus, Ln-5 may play an important role in regulating adhesion and migration in normal and transformed breast epithelium. Our results indicate that the type of integrin utilized by breast cells to interact with Ln-5, as well as its functional state, may determine whether cells will be statically adherent or migratory on Ln-5.
Plopper
G E
GE
Department of Cell Biology/SBR12, The Scripps Research Institute, La Jolla, CA 92037, USA.
Domanico
S Z
SZ
Cirulli
V
V
Kiosses
W B
WB
Quaranta
V
V
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D017931:DNA Primers; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016023:Integrins / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology*; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D016023:Integrins; D000097794:Kalinin