Metastases-related genes in the classification of liver and peritoneal metastasis in human gastric cancer

Introduction. With the aim of identifying metastasesrelated genes in gastric cancer, we performed a broad analysis of differential gene expression between low-metastatic parental cell lines and established highly metastatic sublines. Materials and methods. We established novel cell lines, AZ-H5c, NUGC-3H5, and TMK-1H7, with a high potential of liver metastasis, and AZ-P7a, NUGC-3P4T, and TMK-1P4a, with a high potential of peritoneal metastasis. These cell lines were derived from low-metastatic parental AZ-521, NUGC-3, and TMK-1 cell lines, respectively. Furthermore, to investigate different levels of gene expression implicated in metastatic potentials in gastric cancer, we investigated approximately 2000 expressed genes in each cell line using a DNA microarray. Results. Varieties of genes were up-regulated or down-regulated in highly metastatic liver and peritoneal cell lines. Fifty-eight genes, including the transferrin receptor, ras-related rho, and osteopontin, and 22 genes, including apolipoprotein E and inhibin A-submit, were up-regulated and down-regulated in two or three liver metastatic sublines. On the other hand, 19 genes, the transferrin receptor, c-fos, and RANTES, and 26 genes, including MAC25, PISSLRE, and RNA polymerase, were up-regulated and down-regulated in two or three peritoneal metastatic sublines. Conclusion. How gene expression is implicated in gastric cancer metastasis has never been thoroughly explained, and further studies are necessary to understand the involvement of genes in cancer metastasis more thoroughly. We hope that our highly metastatic liver and peritoneal experimental models are helpful for further study and gene therapy of human gastric cancer. (c) 2005 Elsevier Inc. All rights reserved.