Integrin (α6/β4) Expression in Human Lung Cancer as Monitored by Specific Monoclonal Antibodies

Abstract In this study, the expression of the α6/β4 integrin complex was analyzed in human lung carcinomas both in vitro and in vivo, using two monoclonal antibodies which recognize the integrin subunits α6 (Mab 135-13C) and β4 (Mab 439-9B). Immunoprecipitation patterns obtained from established human lung carcinoma cell lines demonstrated that the α6 and the β4 subunits were differentially expressed in carcinomas of different types. The α6 subunit was expressed in all the cell lines tested (squamous cell carcinoma A431, adenocarcinoma A549, large cell carcinoma DG3, and small cell carcinoma AE2). The β4 subunit was expressed in non-small cell cancer lines but was not detectable in the small cell cancer line tested. Using a quantitative two-site assay, we measured the concentration of the α6/β4 integrin in matched biopsies from primary lung tumors and from normal lung. These studies confirmed that the complex was differentially expressed in non-small versus small cell lung cancers and that it was also detectable in lysates from normal lung at low levels. The highest levels of α6/β4 were found in moderately differentiated squamous cell carcinomas. By immunohistochemistry, the β4 subunit was detectable in all the squamous cell carcinomas and adenocarcinomas tested (a total of 59), but not in 10 small cell cancers. The patterns of immunoreactivity were consistent with the expected distribution of membrane glycoproteins and, in some squamous cell carcinomas, were suggestive of the localization displayed by molecules involved in carcinoma-stroma interaction. Immunohistochemical staining indicated that β4 was also expressed in specific types of nonrespiratory pulmonary epithelial cells.