β1 Integrin Expression on Human Small Cell Lung Cancer Cells

LE Feldman, KC Shin, RB Natale, RF Todd III - Cancer research, 1991 - AACR
LE Feldman, KC Shin, RB Natale, RF Todd III
Cancer research, 1991AACR
The integrins are a supergene family of cell surface glycoproteins that promote cellular
adhesion. Each member of the family is an α/β heterodimer composed of a distinct α subunit
noncovalently linked to one of at least six common β subunits. These include the six β1
integrins (α1–6/β1) which represent receptors for extracellular matrix proteins and the three
β2 integrins (αl, αm, αx/β2 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 β1 …
Abstract
The integrins are a supergene family of cell surface glycoproteins that promote cellular adhesion. Each member of the family is an α/β heterodimer composed of a distinct α subunit noncovalently linked to one of at least six common β subunits. These include the six β1 integrins (α1–61) which represent receptors for extracellular matrix proteins and the three β2 integrins (αl, αm, αx2 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 β1 integrins and that small cell lung cancer (SCLC) cell lines express the β2 integrin Mo1 (αM2). 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 α and β subunit-specific monoclonal antibodies demonstrated the uniform expression of β11 ≫ β2 ≥ β3 ⋍ β4). Among the β1-associated α subunits, α3 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-β1 and anti-α3 immunoprecipitates), while α5 was not detected. The leukocyte (β2-associated) αm and αl subunits were also variably expressed by the five lines. Consistent with the surface expression of β1 integrin gene products, β1 (but not β2) mRNA was detected in SCLC cells by Northern blot analysis. That β1 integrin expression was involved in SCLC adhesion was suggested by the adherence of H345 cells to laminin, a known ligand for the α3β1 integrin. Moreover, an antibody specific for the β1 subunit inhibited this adhesion, indicating that the β1 subunit promotes adhesion to laminin. We conclude that β1 integrin molecules are expressed by human SCLC cells (with uniform expression of α31) and promote their adhesion to laminin.
AACR