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

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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.