IDENTIFICATION OF METASTATIC-RELATED GENES AND A NOVEL APPROACH FOR THE INHIBITION OF METASTASIS USING HUMAN BREAST CANCER CELL LINES

转移相关基因的鉴定和利用人乳腺癌细胞系抑制转移的新方法

• 批准号: 13671317
• 负责人: HATA Fumitake
• 金额: $ 2.18万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671317/
• 关键词: BREAST CANCER; BONE METASTASIS; LUNG METASTASIS; LIVER METASTASIS; LYMPH NODE METASTASIS; ANIMAL MODEL; DNA CHIP; GENE EXPRESSION ANALYSIS

First, many human breast cancer cell lines were purchased from JCRB. They were injected into the breast of mice to establish highly metastatic cell lines. Unfortunately, these parental cell lines had not metastasized to the liver, lymph nodes, and lungs. The cell lines were then injected into the spleen in a manner similar to that used in previous research involving the pancreas and gastric cancer cell lines. In order for the breast cancer cell lines to metastasize to the lymph nodes, lungs, and liver, more time was required. An in vivo selection procedure was used. A highly metastatic cell line to the liver, ZR-H4,(metastatic rate:80%) was established. It originated from the parental breast cancer cell line, ZR75-1,(metastatic rate:10%). In the study period, it was not possible to establish cell lines that were highly metastatic to the lungs, bone, and lymph nodes. ZR75-1 and ZR-H4 are being used in a differential gene expression analysis, which is being conducted with a DNA chip.While establishing breast cancer cell liens that were highly metastatic, differential gene expression was analyzed with the use of pancreatic cancer cell lines. This was done to establish a successful system of gene expression analysis. Tens of genes were identified as candidates that might be related to pancreatic cancer metastasis(J.Exp.Clin.Cancer Res.,2003;22:421-42). More cell lines were used, and several genes were identified as specific to liver and peritoneal metastases in pancreatic cancer. Once cancer cell lines that are highly metastatic to the lungs, lymph nodes, bones, and breast are established, gene expression analysis using a DNA chip will follow. The data are preliminary ; however, the information obtained has potential for clarifying the mechanisms of breast cancer metastasis and for providing a timeframe for the inhibition of cancer metastasis.

首先，许多人乳腺癌细胞系购自JCRB。它们被注射到小鼠的乳房中以建立高转移性细胞系。不幸的是，这些亲本细胞系没有转移到肝脏、淋巴结和肺。然后将细胞系以与先前涉及胰腺癌和胃癌细胞系的研究中使用的类似的方式注射到脾脏中。为了使乳腺癌细胞系转移到淋巴结、肺和肝脏，需要更多的时间。使用体内选择程序。建立了一个高转移性的肝细胞系，ZR-H4，（转移率：80%）。它来源于亲本乳腺癌细胞系ZR 75 -1（转移率：10%）。在研究期间，不可能建立肺、骨和淋巴结高度转移的细胞系。在利用DNA芯片进行的差异基因表达分析中，使用ZR 75 -1和ZR-H4，在建立高转移性乳腺癌细胞系的同时，使用胰腺癌细胞系进行差异基因表达分析。这样做是为了建立一个成功的基因表达分析系统。数十个基因被鉴定为可能与胰腺癌转移相关的候选基因（J.Exp.Clin.Cancer Res.，2003;22：421-42）。使用了更多的细胞系，并鉴定了几个基因对胰腺癌的肝和腹膜转移具有特异性。一旦建立了对肺、淋巴结、骨骼和乳房具有高度转移性的癌细胞系，将使用DNA芯片进行基因表达分析。数据是初步的;然而，所获得的信息有可能澄清乳腺癌转移的机制，并为抑制癌症转移提供时间框架。

项目成果

Ohno K, Hata F, Nishimori H, et al.: "Biological properties and differential gene expression profiles in established highly liver or peritoneal metastatic cell lines of human pancreatic cancer"J.Clin.Exp.Cancer Res.. 22. 623-631 (2004)

Ohno K、Hata F、Nishimori H 等：“已建立的高度肝或腹膜转移的人胰腺癌细胞系的生物学特性和差异基因表达谱”J.Clin.Exp.Cancer Res.. 22. 623-631

Nomura H, Nishimori H, Yasoshima T, Hata F, et al.: "A new liver metastatic and peritoneal dissemination model established from the same human pancreatic cancer cell line : analysis using cDNA macroarray"Clinical & Experimental Metastasis. 19. 391-399 (20

Nomura H、Nishimori H、Yasoshima T、Hata F 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 宏阵列进行分析”临床

Ohno K, Hata F, Nishimori H, Nomura N, Yasoshima T, Nakajima F, Tanaka H, Kitagawa S, Hirai I, Kamiguchi K, Isomura H, Sato N, Denno R, Hirata K.: "Biological properties and differential gene expression profiles in established highly liver or peritoneal m

Ohno K、Hata F、Nishimori H、Nomura N、Yasoshima T、Nakajima F、Tanaka H、Kitakawa S、Hirai I、Kamiguchi K、Isomura H、Sato N、Denno R、Hirata K.：“生物学特性和差异基因表达

Nakajima F, Nishimori H, Hata F, et al.: "Gene Expression Screening using cDNA Macroarray for Clarification of the Mechanisms of Peritoneal Dissemination of Pancreatic Cancer"Surgery Today. (in press).

Nakajima F、Nishimori H、Hata F 等人：“使用 cDNA 宏阵列进行基因表达筛选，以阐明胰腺癌腹膜播散的机制”《今日外科》。

Tanaka H, Hata F, Nishimori H, Honmou O, Yasoshima T, Nomura H, Nakajima F, Hirai H, Kamiguchi K, Hirohashi Y, Sato N, Denno R, Hirata K.: "Differential Gene Expression Screening Between Parental and Highly Metastatic Pancreatic Cancer Variants Using a DN

Tanaka H、Hata F、Nishimori H、Honmou O、Yasoshima T、Nomura H、Nakajima F、Hirai H、Kamiguchi K、Hirohashi Y、Sato N、Denno R、Hirata K.：“亲本和高转移性之间的差异基因表达筛选