Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas

The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha 3 and alpha 6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta 1 and beta 4 subunits, the beta 1C splice variant of beta 1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. Al carcinomas expressed alpha 3 extensively; alpha 3 expression predominated (40 of 40) over alpha 6 (25 of 40). In all alpha 6-positive carcinomas, alpha 6A was expressed, whereas alpha 6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha 3 and of the A or B intracytoplasmic domains of alpha 6 were shown. Notably, in normal bronchial epithelium, alpha 6 colocalized with beta 4, whereas in the tumors, alpha 6A frequently overlapped with beta 1 in a circumferential pattern; alpha 6 beta 1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta 4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta 1C and Ki-67. The prevalence of alpha 6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha 6B prevails, and alpha 6 predominates over alpha 3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of a3 over alpha 6 and of alpha 6A over alpha 6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas. Copyright (C) 1998 by W.B. Suanders Company.