In vitro regulation of human breast cancer cell adhesion and invasion via integrin receptors to the extracellular matrix.
The extracellular matrix consists of the interstitium and the basement membrane. Cellular interaction with fibronectin, laminin and collagen provides a possible mechanism by which cancer cells adhere, invade and metastasize. The integrins are a major family of adhesion molecules that recognize epitopes on the extracellular matrix as ligands. These include the alpha 2 beta 1, alpha 3 beta 1, alpha v beta 1 and alpha v beta 5 integrins, most of which were found to be expressed on MCF-7, T47D, MDA-MB-231, ZR75-1 and Hs578T breast cancer cell lines. Each cell line adhered to the matrix proteins in a dose-dependent manner and was inhibited by monoclonal antibodies against relevant integrins. Only Hs578T was significantly invasive through fibronectin but both Hs578T and MDA-MB-231 invaded through laminin and type IV collagen in an in vitro assay. The invasive potential of these cell lines could be inhibited by integrin antibodies added to cells before incubation, but the addition of antibodies after cells were allowed to adhere to the matrix failed to inhibit invasion. Inhibition of cellular adhesion to the matrix reduced the invasive potential of breast cancer cell lines. As integrin antibodies inhibit cell invasion in vitro, the integrins may be of potential value as antitumour therapeutic agents.
Gui
G P
GP
Department of Surgery, St Bartholomew's Hospital, UK.
Puddefoot
J R
JR
Vinson
G P
GP
Wells
C A
CA
Carpenter
R
R
D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion; D002455:Cell Division; D003094:Collagen; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005353:Fibronectins; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007797:Laminin; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D003094:Collagen