Analysis of gene expressions involved in cancer-host cells cross talk at the invasion front of nonsmall cell lung cancer

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It is recently proposed that cancer cells make microenvironment suitable for their invasion through cross talk with host cells. To elucidate genes or molecules involved in the cancer cell-host cell cross talk at the invasion front of nonsmall cell lung cancer (NSCLC), mRNA profilings of 1176 cancer-related genes at the invasion front tissues of NSCLCs of various progressions were analyzed by cDNA macroarray system (Cancer array 1.2, Clontech). 121 genes, including cyclin D1, c-myc, insulin-like growth factor, rho-associated GTP binding proteins, laminin receptor, DNA polymerases, beta-catenin, wnt 8B, elongation factor alpha-1, were commonly overexpressed in NSCLC tissues. Ten genes, such as membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-3, p21-rac1, vascular endothelial growth factor (VEGF), jagged-1, jagged-2, notch-4, c-fos related antigen, were overexpressed both in squamous cell carcinomas and high stage-adenocarcinomas compared with low stage-adenocarcinomas, while ezrin (villin 2) and macrophage inhibitory cytokine (MTC)-1 genes did the opposite. These results were confirmed by real time RT-PCR using TaqMann-probe method. These data suggested that rac-1/MT1-MMP, jagged-1, -2/ notch-4, p53 / MIC-1 groups may actively involved in the cross talk between lung cancer and host cells and works either positively or negatively to make appropriate microenvironment for invasion of the lung cancer cells. We have also established laser-captured microdissection / real time RT-PCR method in order to analyze gene expressions more in detail at the invasion front of NSCLCs. Furthermore, functional and non-invasive examination methods of gene expressions in NSCLC tissues in vivo were tried successfully using FDG- and MIBI-PET. Present results may contribute to estimate biological features of NSCLCs and establish adequate therapy for lung cancer patients.