BETA-1 INTEGRIN EXPRESSION ON HUMAN SMALL-CELL LUNG-CANCER CELLS

The integrins are a supergene family of cell surface glycoproteins that promote cellular adhesion. Each member of the family is an alpha-beta heterodimer composed of a distinct alpha-subunit noncovalently linked to one of at least six common beta-subunits. These include the six beta-1 integrins (alpha-1-6/beta-1) which represent receptors for extracellular matrix proteins and the three beta-2 integrins (alpha-L, alpha-M, alpha-X/beta-2) that are expressed by leukocytes and which bind to C3bi and/or endothelial ligands. Recently, it was reported that certain human tumor cells express the beta-1 integrins and that small cell lung cancer (SCLC) cell lines express the beta-2 integrin Mo1 (alpha-M/beta-2). To extend these initial observations, we examined SCLC cell lines for integrin expression at the glycoprotein and mRNA levels and assessed the potential function of these integrins in promoting SCLC adhesion. An indirect immunofluorescence analysis of five SCLC cell lines (NCI-H187, H345, H146, H209, and N417) using alpha and beta-subunit-specific monoclonal antibodies demonstrated the uniform expression of beta-1 (beta-1 >> beta-2 greater-than-or-equal-to beta-3 congruent-to beta-4). Among the beta-1-associated alpha-subunits, alpha-3 was uniformly expressed at high surface density by all five cell lines (as confirmed in H345 cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of anti-beta-1 and anti-alpha-3 immunoprecipitates), while alpha-5 was not detected. The leukocyte (beta-2-associated) alpha-M and alpha-L subunits were also variably expressed by the five lines. Consistent with the surface expression of beta-1 integrin gene products, beta-1 (but not beta-2) mRNA was detected in SCLC cells by Northern blot analysis. That beta-1 integrin expression was involved in SCLC adhesion was suggested by the adherence of H345 cells to laminin, a known ligand for the alpha-3-beta-1 integrin. Moreover, an antibody specific for the beta-1 subunit inhibited this adhesion, indicating that the beta-1 subunit promotes adhesion to laminin. We conclude that beta-1 integrin molecules are expressed by human SCLC cells (with uniform expression of alpha-3/beta-1) and promote their adhesion to laminin.