LOSS OF ALPHA(1)BETA(1) AND REDUCED EXPRESSION OF OTHER BETA(1)-INTEGRINS AND CAM IN LUNG ADENOCARCINOMA COMPARED WITH PNEUMOCYTES

Alterations in expression of various cell-adhesion molecules have been reported in a variety of malignant tissues. However, little is known about how lung adenocarcinomas differ in CAM expression from the norma l lung. We analyzed the expression of integrins alpha1beta1 through al pha6beta1, intercellular adhesion molecule (ICAM)-1, neural cell adhes ion molecule (NCAM), and lymphocyte function antigen (LFA)-3, CD44, an d the two carbohydrate antigens, Lewis(x) (Le(x)) and sialosyl-Le-Le(x ) of lung adenocarcinoma cells, and compared them with autologous pneu mocytes. CAM expression was studied by an immunohistochemical method u sing monoclonal antibodies, and computerized image analysis was used t o quantify the immunoperoxidase-staining intensity. The normal lung al veolar cells strongly expressed the integrins alpha1beta1 and alpha3be ta1, and fairly expressed alpha2beta1, alpha4beta1, alpha5beta1, and a lpha6beta1. ICAM-1, LFA-3, and CD44 were strongly expressed, whereas N CAM, the Le(x) and sialosyl-Le-Le(x) antigens, were expressed weakly. In contrast, we did not detect expression of the alpha1beta1 integrin on any autologous lung adenocarcinoma cells, and they showed on averag e a 50% reduction in labeling relative intensity units for the integri n common chain marker beta1, the specific integrins alpha3beta1, alpha 5beta1, and alpha6beta1, and ICAM-1, and LFA-3. Examination of the adj acent small blood vessel endothelium in malignant lung tissues did not reveal any major alterations in CAM expression, the small vessel endo thelium of the normal and malignant lung tissues appeared with a simil ar CAM profile. These results suggest that lung adenocarcinoma cells h ave a lack of alpha1beta1, expression and significant reduction in som e other integrin beta1 and CAM expression in comparison with their aut ologous pneumocytes. This aberration in CAM expression by the lung ade nocarcinoma cells may be involved in their loss of proliferation contr ol and may interfere with leukocyte adhesion to tumor cells, enabling the tumor to escape immunodestruction. (C) 1994 Wiley-Liss, Inc.