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 α3 and α6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to β1 and β4 subunits, the β1C splice variant of β1, 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. All carcinomas expressed α3 extensively; α3 expression predominated (40 of 40) over α6 (25 of 40). In all α6-positive carcinomas, α6A was expressed, whereas α6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of α3 and of the A or B intracytoplasmic domains of α6 were shown. Notably, in normal bronchial epithelium, α6 colocalized with β4, whereas in the tumors, α6A frequently overlapped with β1 in a circumferential pattern; α6β1 coexpression was also shown by coprecipitation experiments. Strung and extensive β4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of β1C and Ki-67. The prevalence of α6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which α6B prevails, and α6 predominates over α3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of α3 over α6 and of α6A over α6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.