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Advances in Brief |
Genome Science Division [Y. H., M. I., H. T., S. T., H. A.], Division of Molecular Biology and Medicine [T. K.], Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan, and First Department of Surgery, Osaka City University Medical School, Osaka 545-8586, Japan [M. Y., K. H.]
Scirrhous gastric cancer is often accompanied by metastasis to the
peritoneum and/or lymph nodes, resulting in the highest mortality rate
among gastric cancers. Mechanisms involved in gastric cancer metastasis
are not fully clarified because metastasis involves multiple steps and
requires the accumulation of altered expression of many different
genes. Thus, independent analysis of any single gene would be
insufficient to understand all of the aspects of gastric cancer
metastasis. In this study, we performed global analysis on
differential gene expression of a scirrhous gastric cancer cell line
(OCUM-2M) and its derivative sublines with high potential for
metastasis to the peritoneal cavity (OCUM-2MD3) and lymph nodes
(OCUM-2MLN) in a nude mice model. By applying a high-density
oligonucleotide array method, expression of approximately 6800 genes
was analyzed, and selected genes were confirmed by the Northern blot
method. In our observations in OCUM-2MD3 cells, 12 genes were
up-regulated, and 20 genes were down-regulated. In OCUM-2MLN cells,
five genes were up-regulated, and five genes were down-regulated. The
analysis revealed two functional gene clusters with altered expression:
(a) down-regulation of a cluster of squamous cell
differentiation marker genes such as small proline-rich proteins
[SPRRs (SPRR1A, SPRR1B, and SPRR2A], annexin A1, epithelial membrane
protein 1, cellular retinoic acid-binding protein 2, and mesothelin in
OCUM-2MD3 cells; and (b) up-regulation of a cluster of
antigen-presenting genes such as MHC class II (DP, DR, and DM) and
invariant chain (Ii) in OCUM-2MLN cells through up-regulation of CIITA
(MHC class II transactivator). We then analyzed six gastric
cancer cell lines by Northern blot and observed preferential
up-regulation of trefoil factor 1, 
-1-antitrypsin, and galectin 4
and down-regulation of cytidine deaminase in cells prone to peritoneal
dissemination. Genes highly correlated with invasion or peritoneal
dissemination of gastric cancer, such as E-cadherin or integrin
ß4, were down-regulated in both of the derivative cell
lines analyzed in this study. This is the first demonstration of global
gene expression analysis of gastric cancer cells with different
metastatic potentials, and these results provide a new insight in the
study of human gastric cancer metastasis.
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