INVESTIGATION FOR CANCER METASTASIS USING METASTATIC HUMAN DIGESTIVE CANCER CELL LINES

使用转移性人类消化癌细胞系研究癌症转移

• 批准号: 12671239
• 负责人: DENNO Ryuichi
• 金额: $ 1.15万
• 依托单位: SAPPORO 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671239/
• 关键词: GASTRIC CANCER; PANCREATIC CANCER; LIVER METASTASIS; PERITONEAL DISSEMINATION; LYMPH NODE METASTASIS; ANIMAL MODEL; CELL LINE; DNA CHIP; 腹膜転移

We established novel gastric cancer sublines (AZ-H5c, NUGC-3H5, TMK-1H7) and pancreatic cancer sublines (HPC-1H5, HPC-3H4, HPC-4H4, Panc-1H5) with a high potential for liver metastasis, and AZ-P7a, NUGC-3P4T, TMK-1P4a (gastric lines) and HPC-1P5a, HPC-3P4a, HPC-4P4a, Panc-1P5a (pancreatic lines) with a high potential for peritoneal metastasis derived from parental low-metastatic AZ-521, NUGC-3, THK-1, HPC-1, HPC-3, HPC-4 and Panc-1 cell lines, respectively. Using these established cell lines, we investigated the biological properties in hematogenous and peritoneal metastasis. Our studies suggested that hematogenous metastasis and peritoneal dissemination have assured biological differences. Moreover, angiogenetic factors in hematogenous metastasis and enhanced motile activity in peritoneal dissemination were closely implicated in the development of these two types of metastasis in digestive cancer. In addition, to clarify the molecular mechanisms of cancer metastasis and of the differe … More nt levels of gene expression in a variety of metastatic potentials in digestive cancer, differential gene expression analysis between parental cell lines and metastatic sublines, and between the metastasis sublines were performed.We analyzed thousands of expressed genes in each cell line by DNA chip. In comparison with each parental cell lines, a large number of genes were up regulated or down-regulated in the cell lines highly metastatic to the liver and peritoneum. In addition, in pancreatic cancer, gene expression profiling analysis clarified 22 genes including FGF-5, matrilysin and so on, that could be used to classify the liver and peritoneal metastases. In gastrice cancer, 24 genes, Integrin3, cadherin and so on, were distinguished to classify the liver and peritoneal metastases.Further studies should be needed to understand more thoroughly the involvement of angiogenetic factors, motile activity and differential expressed genes in cancer metastasis. However, these results will help to clarify the biological and molecular mechanisms of digestive cancer metastases. Moreover, genes revealed by profiling analysis will be novel molecular markers to predict whether some pancreatic and/or gastric cancers develop liver or peritoneal metastasis after curative resection. Less

我们分别从亲代低转移性的AZ-521、NUGC-3、THK-1、HPC-1、HPC-3、HPC-1细胞系建立了具有高肝转移潜力的新型胃癌亚系（AZ-H5c、NUGC-3H5、tmk - 1h4、Panc-1H5）和具有高腹膜转移潜力的胰腺亚系（AZ-P7a、NUGC-3P4T、TMK-1P4a）和HPC-1P5a、HPC-3P4a、HPC-4P4a、Panc-1P5a)。利用这些已建立的细胞系，我们研究了血液和腹膜转移的生物学特性。我们的研究表明，血液转移和腹膜播散有一定的生物学差异。此外，血液转移中的血管生成因子和腹膜播散中的运动活性增强与这两种消化道肿瘤转移的发生密切相关。此外，为了阐明消化道癌转移的分子机制和不同类型转移电位中基因表达水平的差异，我们进行了亲本细胞系与转移亚系之间以及转移亚系之间基因表达的差异分析。我们用DNA芯片分析了每个细胞系中数千个表达基因。与各亲本细胞系相比，肝脏和腹膜高度转移细胞系中大量基因上调或下调。此外，在胰腺癌中，基因表达谱分析明确了FGF-5、基质溶素等22个基因，可用于肝转移和腹膜转移的分类。在胃癌中，通过整合素3 （Integrin3）、钙粘蛋白（cadherin）等24个基因对肝转移和腹膜转移进行分类。需要进一步的研究来更深入地了解血管生成因子、运动活性和差异表达基因在肿瘤转移中的作用。然而，这些结果将有助于阐明消化道肿瘤转移的生物学和分子机制。此外，基因谱分析揭示的基因将成为预测一些胰腺癌和/或胃癌在根治性切除后是否发生肝脏或腹膜转移的新的分子标记。少

项目成果

Nomura H, Nishimori H, Yasoshima T, Hata E. et al.: "A new liver metastatic and peritoneal dissemination model established from the same human pancreatic cancer cell line : analysis using cDNA"Clinical & Experimental Metastasis. 19. 391-399 (2002)

Nomura H、Nishimori H、Yasoshima T、Hata E.等人：“从同一人类胰腺癌细胞系建立的新的肝转移和腹膜传播模型：使用cDNA进行分析”临床

Nakajima F, Nishimori H, Hata F, Yasoshima T, Nomura H, Tanaka H, Ohno K, Yanai Y, Kamiguchi K, Sato N, Denno R, Hirata K: "Gene Expression Screening using cDNA Macroarray for Clarification of the Mechanisms of Peritoneal Dissemination of Pancreatic Cance

Nakajima F、Nishimori H、Hata F、Yasoshima T、Nomura H、Tanaka H、Ohno K、Yanai Y、Kamiguchi K、Sato N、Denno R、Hirata K：“使用 cDNA 宏阵列进行基因表达筛选，以阐明腹膜的机制

Nomura, H., Nishimori, H., Yasoshima, T., Hata, F., Sogahata, K., Tanaka, H., Nakajima, F., Ikeda, S., Kamiguchi, K., Isomura, H., Sato, N., Denno, R., Hirata, K.: "A new experimental mouse model of peritoneal dissemination of human gastric cancer cells :

野村 H.、西森 H.、八岛 T.、畑 F.、曾畑 K.、田中 H.、中岛 F.、池田 S.、上口 K.、矶村 H.、

Nomura H.: "a new experimental mouse model of peritoneal dissemination of human gastric cancer cells : analysis of the mechanism of peritoneal dissemination using cDNA macroarrays"Jpn. J. Cancer Res.. 92. 748-754 (2001)

Nomura H.：“人胃癌细胞腹膜传播的新实验小鼠模型：使用cDNA宏阵列分析腹膜传播的机制”Jpn。

Nishimori H,Yasoshima T,Denno R,Shishido T,Hata F,Honma T,Ura H,Yamaguchi K,Yagihashi A,Tanaka H,Kawaguchi S,Kamiguchi K,Isomura H,Sato N and Hirata K.: "A new peritoneal dissemination model established from the human pancreatic cancer cell line."Pancreas

Nishimori H、Yasoshima T、Denno R、Shishido T、Hata F、Honma T、Ura H、Yamaguchi K、Yagihashi A、Tanaka H、Kawaguchi S、Kamiguchi K、Isomura H、Sato N 和 Hirata K.：“一种新的腹膜