Integrins are heterodimeric transmembrane receptors consisting of 18 alpha and 8 beta subunits. Heterodimer composition of alpha and beta subunits has a potential for determining tumor subtypes of human lung cancer. The purpose of this study was to investigate the expression profile of integrins in lung cancer cells. Expression profiling of integrins in a panel of lung cancer cell line, including A549 (adenocarcinoma, ADC), Calu-1 (squamous carcinoma, SCC), H1650 (bronchioloalveolar carcinoma, BAC) and DMS-53 (small cell lung cancer, SCLC), was analyzed by cDNA microarrays, restriction analysis of gene expression (RAGE) and flow cytometry. Seventy-nine lung cancer specimens were used to further validate the data from cell lines using immunohistochemistry. Integrins are obviously expressed in a cell type-specific manner, such as alpha 3 in A549, Calu-1 and H1650 except in DMS53, alpha 4 in H1650, alpha 5 and beta 1 in all cell lines. The integrins detected with cDNA microarrays were all unequivocally detected with RAGE and by flow cytometry at the protein level. In all lung cancer specimens, alpha 3 integrin was strongly expressed in ADC, SCC and BAC, but was infrequent in SCLC. alpha 4 integrin was solely expressed in BAC. alpha 5 and beta 1 integrins were expressed in all four histological types of lung cancer specimens. Integrin alpha 3 and alpha 4 may be useful as diagnostic markers for adenocarcinoma, squamous cell carcinoma and bronchioloalveolar carcinoma. RAGE is a promising technique for studying the expression profiles of genes, such as integrins in cancer cells. (C) 2009 Elsevier GmbH. All rights reserved.