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

非小细胞肺癌侵袭前沿癌症与宿主细胞串扰相关基因表达分析

• 批准号: 13670192
• 负责人: UEDA Yoshimichi
• 金额: $ 2.11万
• 依托单位: KANAZAWA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670192/
• 关键词: Lung cancer; Invasion and metastasis; mRNA profiling; cDNA macroarray; Real time RT-PCR; Laser-captured microdissection; FDG-PET; MIBI-PET; リアルタイムRT-PCR法; Laser microdissection法; 定量RT-PCR法; Jagged-1; Villin 2; DNAマクロアレイ; プログレッション; in situ g

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.

最近，有人提出，通过与宿主细胞进行串扰，癌细胞使微环境适合其侵袭。为了阐明在nonsmall细胞肺癌的入侵前面参与癌症细胞宿主细胞串扰（NSCLC）的基因或分子，通过CDNA MacroArray System（cancer cancroarray System 1.2，clontech，Clontech）分析了各种进展的NSCLCS的1176个与癌症相关基因的mRNA分析。 121个基因，包括细胞周期蛋白D1，C-MYC，胰岛素样生长因子，RHO相关的GTP结合蛋白，层粘连蛋白受体，DNA聚合酶，β-catenin，Wnt 8b，延长因子Alpha-1在NSCLC组织中通常过表达。十个基因，例如膜型1基质金属蛋白酶（MT1-MMP），MMP-3，P21-RAC1，血管内皮生长因子（VEGF）（VEGF），JAGGED-1，JAGGED-2，JAGGED-2，NOTCH-4，NOTCH-4，C-FOS相关的相关抗原，高度表达了高阶段的高阶段和高级抗原。阶段 - 腺癌，而ezrin（Villin 2）和巨噬细胞抑制细胞因子（MTC）-1基因相反。使用TAQMANN-PROBE方法通过实时RT-PCR证实了这些结果。这些数据表明，RAC-1/ MT1-MMP，JAGGED-1，-2/ NOTCH-4，p53/ MIC-1组可能会积极参与肺癌与宿主细胞之间的串扰，并积极或负面地工作以使适当的微环境侵入肺癌细胞。我们还建立了激光捕获的显微解剖 /实时RT-PCR方法，以便在NSCLCS的入侵方面对基因表达进行更详细的详细分析。此外，使用FDG-和MIBI-PET成功尝试了NSCLC组织中基因表达的功能和非侵入性检查方法。目前的结果可能有助于估计NSCLC的生物学特征，并为肺癌患者建立足够的治疗。

项目成果

Kotaro Higashi et al.: "Value of whole-body FDG PET in management of lung cancer"Ann. Nucl. Med.. 17・1. 1-14 (2003)

Kotaro Higashi 等：“全身 FDG PET 在肺癌治疗中的价值”Ann. 17・1 (2003)。

Jinshan Zhou: "Expression of multidrug resistence protein and mRNA correlate with 99mTc-MIBI imaging in patients with lung cancer"J. Nuci. Med.. 42・10. 1476-1483 (2001)

周金山：“肺癌患者中多药耐药蛋白的表达及其与 99mTc-MIBI 成像的相关性”J. Nuci. 1476-1483 (2001)。

Jinshan Zhou et al.: "Expression of multidrug resistence protein and mRNA correlate with 99mTc-MIBI imaging in patients with lung cancer"J. Nucl. Med.. 42・10. 1476-1483 (2001)

Jinshan Zhou 等：“肺癌患者中多药耐药蛋白和 mRNA 的表达与 99mTc-MIBI 成像相关”J. Nucl. 1476-1483 (2001)。

Jinshan Zhou, Kotaro Higashi, Yoshimichi Ueda, Yuko Kodama, Dachuan Guo, Fumiko Jisaki, Aya Sakurai, Tsutomu Takegami, Shogo Katsuda, and Itaru Yamamoto: "Expression of multidrug resistance protein and messenger RNA correlate with 99mTc-MIBI imaging in pa

Jinshan Zhou、Kotaro Higashi、Yoshimichi Ueda、Yuko Kodama、Dachuanuo、Fumiko Jisaki、Aya Sakurai、Tsutomu Takegami、Shogo Katsuda 和 Itaru Yamamoto：“多药耐药蛋白和信使 RNA 的表达与 99mTc-MIBI 成像相关

Kotaro Higashi, Ichiro Matsunari, Yoshimichi Ueda, Ryosuke Ikeda, Jinfei Guo, Manabu Oguchi, Hisao Tonami and Itaru Yamamoto: "Value of whole-body FDG PET in management of lung cancer."Ann. Nucl. Med.. 17(1). 1-14 (2003)

Kotaro Higashi、Ichiro Matsunari、Yoshimichi Ueda、Ryosuke Ikeda、Jinfeiuo、Manabu Oguchi、Hisao Tonami 和 Itaru Yamamoto：“全身 FDG PET 在肺癌治疗中的价值。”Ann。