Loss of α₁β₁ and reduced expression of other β₁ integrins and cam in lung adenocarcinoma compared with pneumocytes

Abstract

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 normal lung. We analyzed the expression of integrins alpha 1 beta 1 through alpha 6 beta 1, intercellular adhesion molecule (ICAM)-1, neural cell adhesion molecule (NCAM), and lymphocyte function antigen (LFA)-3, CD44, and the two carbohydrate antigens, Lewisx (Le(x)) and sialosyl-Le-Le(x) of lung adenocarcinoma cells, and compared them with autologous pneumocytes. CAM expression was studied by an immunohistochemical method using monoclonal antibodies, and computerized image analysis was used to quantify the immunoperoxidase-staining intensity. The normal lung alveolar cells strongly expressed the integrins alpha 1 beta 1 and alpha 3 beta 1, and fairly expressed alpha 2 beta 1, alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1. ICAM-1, LFA-3, and CD44 were strongly expressed, whereas NCAM, the Le(x) and sialosyl-Le-Le(x) antigens, were expressed weakly. In contrast, we did not detect expression of the alpha 1 beta 1 integrin on any autologous lung adenocarcinoma cells, and they showed on average a 50% reduction in labeling relative intensity units for the integrin common chain marker beta 1, the specific integrins alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1, and ICAM-1, and LFA-3. Examination of the adjacent small blood vessel endothelium in malignant lung tissues did not reveal any major alterations in CAM expression, the small vessel endothelium of the normal and malignant lung tissues appeared with a similar CAM profile. These results suggest that lung adenocarcioma cells have a lack of alpha 1 beta 1 expression and significant reduction in some other integrin beta 1 and CAM expression in comparison with their autologous pneumocytes. This aberration in CAM expression by the lung adenocarcinoma cells may be involved in their loss of proliferation control and may interfere with leukocyte adhesion to tumor cells, enabling the tumor to escape immunodestruction.

Expression of CD44 isoforms during bleomycin-or radiation-induced pulmonary fibrosis in rats and mini-pigs

“…In a recent study, Roussel et al (1994) reported that transformation of normal alveolar pneumocytes to a malignant phenotype was associated with a loss of integrins and CAMs. CD44 was shown to be expressed in non-small cell lung tumours, squamous metaplasia, basal bronchial epithelial cells and activated type II pneumocytes (Penno et al 1994;Terpe et al 1993Terpe et al , 1994.…”

Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo

“…Actually, integrins are heterodimeric transmembrane molecules that modulate cell adhesion, and consistently reduced expression or altered distribution of such molecules has been reported in colon, lung, pancreas and breast tumors. [38][39][40][41] It is also noteworthy that transfection of the highly metastatic BL6 melanoma cells 42 with the integrin a4 subunit gene was reported to inhibit their metastatic potential in vivo. 19 Concerning the other targeted gene, the dok5 gene, it has been previously shown that another member of the dok family, dok1, positively regulates B16F10 cell mobility ex vivo.…”

Mechanisms of tumor metastasis: cell biological aspects and clinical implications

“…By immunohistochemistry, many tumors have been analyzed for the expression and distribution of integrins in comparison to their respective normal tissue counterpart. Despite many heterogeneous results, consistent patterns such as reduced expression or altered distribution of collagen and laminin receptors were observed in colon, lung, pancreas, and breast cancers (Stallmach et al 1992;Roussel et al 1994;Weinel et al 1995;Gui et al 1996). Since laminin and collagen receptors play an important role in attaching cells to the basement membrane, these results suggest that loss of attachment to the basement membrane might be important in tumor development.…”