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Increasing evidence suggests that changes in the tumour cell microenvironment contribute to tumorigenesis and metastasis, but the molecular basis of these alterations is not well understood. Recent reports indicated that carcinoma-associated fibroblasts (CAFs) derived from invasive human breast carcinomas have greater ability to promote the growth of mammary carcinoma cells and to enhance tumor angiogenesis compared to fibroblasts derived from corresponding non-tumor areas (CPs). We have investigated the influence of lung CAFs and CPs on the growth of A549 and H460 non-small cell lung carcinoma cells in immune deficient mice. Using in vivo xenograft model, CAFs demonstrated significantly enhanced ability to stimulate the tumor formation of lung cancer cell lines. Co-cultured of CAFs but not CPs with human lung cancer cell lines also showed the induction of an active form of MMP-2 and activation of transcription factor NF-κB in fibroblasts. Genome wide expression profiling studies may reveal genes that mediate the stromal factor important in the progression of non-small cell lung cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA