Integrins are thought to have a central role in tumor-stromal communication. Our group previously reported that integrin α11 (ITGA11) is frequently overexpressed in non-small cell lung cancer (Oncogene 21: 7598-7604, 2002). Using laser capture microdissection, we demonstrated that ITGA11 mRNA is expressed in both the carcinoma and stromal fibroblast cells. However, immunofluorescent studies demonstrated that the ITGA11 protein is mainly expressed in the stroma. We hypothesized that stromal ITGA11 expression plays an important role in regulating the growth of lung cancer cells. To test this hypothesis, we co-implanted into SCID mice A549 lung adenocarcinoma cells with either SV40 immortalized embryonic fibroblasts derived from ITA11 knocked-out (KO) mice, or with similarly immortalized normal/wild type (WT) embryonic fibroblasts. A549 cells, KO fibroblasts and WT fibroblasts were used as controls. Tumor growth was closely monitored for 4 weeks. The A549, WT fibroblast and KO fibroblast cell lines individually formed small carcinoma and sarcomas, respectively. The co-implantation of A549 with both WT and KO fibroblasts increased tumor growth, but tumors formed by the A549/WT fibroblasts were significantly greater than those formed by A549/KO fibroblasts. The carcinoma cells of A549/WT and A549/KO tumors appeared to demonstrate greater differentiation compared to A549 controls. Assays of ITGA11 mRNA expression in primary and metastatic tumors of an orthotopic human lung cancer model in nude rats demonstrate higher levels of stromal (rat) ITGA-11 in the metastatic than primary sites. The findings suggest that ITGA11 expression in tumor stroma fibroblast cells may affect the growth and metastasis of lung carcinoma cells. ITGA may represent a novel candidate for targeted therapy in non-small cell lung cancer. (Supported by Canadian Cancer Society grant #015184)

[Proc Amer Assoc Cancer Res, Volume 46, 2005]