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

首先，许多人类乳腺癌细胞系是从JCRB购买的。他们被注射到小鼠的乳房中，以建立高度转移的细胞系。不幸的是，这些亲代细胞系没有转移到肝脏、淋巴结和肺部。然后将这些细胞系注射到脾脏中，方法与之前研究胰腺癌和胃癌细胞系时使用的方法类似。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。采用体内筛选程序。建立了肝脏高转移细胞系ZR-H4（转移率：80%）。它起源于亲本乳腺癌细胞系ZR75-1（转移率：10%）。在研究期间，不可能建立高度转移到肺、骨和淋巴结的细胞系。ZR75-1和ZR-H4被用于通过DNA芯片进行的差异基因表达分析。在建立高度转移的乳腺癌细胞系的同时，利用胰腺癌细胞系分析了差异基因表达。这样做是为了建立一个成功的基因表达分析系统。数十个基因被确定为可能与胰腺癌转移有关的候选基因（j . exp . clint）。癌症Res。2003;22:421-42)。使用了更多的细胞系，并确定了几个基因对胰腺癌的肝脏和腹膜转移具有特异性。一旦建立了高度转移到肺部、淋巴结、骨骼和乳房的癌细胞系，就会使用DNA芯片进行基因表达分析。这些数据是初步的；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一个时间框架。

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.