Human colon carcinoma cells use multiple receptors to adhere to laminin: involvement of alpha 6 beta 4 and alpha 2 beta 1 integrins.
In this study, we used clone A, a human colon carcinoma cell line, to characterize those integrins that mediate colon carcinoma adhesion to laminin. Monoclonal antibodies specific for the human beta 1 subunit inhibited clone A adhesion to laminin. They also precipitated a complex of surface proteins that exhibited an electrophoretic behavior characteristic of alpha 2 beta 1 and alpha 3 beta 1. A monoclonal antibody specific for alpha 2 (PIH5) blocked clone A adhesion to laminin, as well as to collagen I. An alpha 3-specific antibody (P1B5) had no effect on clone A adhesion to laminin, even though it can block the adhesion of other cell types to laminin. Thus, the alpha 2 beta 1 integrin can function as both a laminin and collagen I receptor on clone A cells. Although these cells express alpha 3 beta 1, an established laminin receptor, they do not appear to use it to mediate laminin adhesion. In addition, the monoclonal antibody GoH3, which recognizes the alpha 6 integrin subunit, also inhibited carcinoma adhesion to laminin but not to fibronectin or collagen I. This antibody precipitated the alpha 6 subunit in association with the beta 4 subunit. There was no evidence of alpha 6 beta 1 association on these cells. In summary, the results obtained in this study indicate that multiple integrin alpha subunits, in association with two distinct beta subunits, are involved in colon carcinoma adhesion to laminin. Based on the behavior of alpha 3 beta 1 and alpha 2 beta 1, the results also suggest that cells can regulate the ability of a specific integrin to mediate adhesion.
Lotz
M M
MM
Laboratory of Cancer Biology, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02115.
Korzelius
C A
CA
Mercurio
A M
AM
D000230:Adenocarcinoma / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007797:Laminin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D003094:Collagen