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

最近提出，癌细胞通过与宿主细胞的串扰来制造适合其侵袭的微环境。为了阐明参与非小细胞肺癌（NSCLC）侵袭前沿癌细胞-宿主细胞串扰的基因或分子，通过cDNA宏阵列系统（Cancer array 1.2，Clontech）分析了不同进展的NSCLC侵袭前沿组织中1176个癌症相关基因的mRNA谱。121个基因，包括cyclin D1、c-myc、胰岛素样生长因子、rho-associated GTP binding proteins、层粘连蛋白受体、DNA聚合酶、β-catenin、wnt 8B、延伸因子α-1，在NSCLC组织中普遍过表达。膜型基质金属蛋白酶1（MT 1-MMP）、MMP-3、p21-rac 1、血管内皮生长因子（VEGF）、jagged-1、jagged-2、notch-4、c-fos相关抗原等10个基因在鳞癌和高分期腺癌中的表达均高于低分期腺癌，而ezrin（villin 2）和巨噬细胞抑制因子（MTC）-1基因的表达则相反。这些结果通过使用TaqMann探针法的真实的时间RT-PCR证实。这些数据表明，rac-1/MT 1-MMP，jagged-1，-2/ notch-4，p53 / MIC-1基团可能积极参与肺癌与宿主细胞之间的串扰，并积极或消极地为肺癌细胞的侵袭创造适当的微环境。我们还建立了激光捕获显微切割/真实的时间RT-PCR方法，以便更详细地分析NSCLC侵袭前沿的基因表达。此外，功能和非侵入性的检测方法在体内的基因表达在NSCLC组织中成功地尝试使用FDG-和MIBI-PET。本研究结果可能有助于评估非小细胞肺癌的生物学特性，并建立适当的治疗肺癌患者。

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.