The Different Expression of Metastasis Related Molecules in the Primary and Metastatic Tumors of Human Colorectal Cancer -Interrelationship between Cancer Cells and Stromal Tissues-

Shun-ichi Ishigami, Shigeki Arii, Tomika Harada, Masaki Mizumoto, Akira Mori, Kouji Hanaki, Yoshihisa Takeda, Hisashi Onodera, Masayuki Imamura

First Department of Surgery, Faculty of Medicine, Kyoto University

The expression of vascular endothelial growth factor (VEFG), matrix metalloproteinase (MMP)-2, -9, and membrane type matrix metalloproteinase (MT1-MMP) in surgical specimens of 74 colorectal cancer patients were evaluated by Northern hybridization and immunohistochemistry, and the difference between primary tumors and metastatic tumors was investigated. The expression of mRNA of these 4 molecules in the primary tumors with liver metastasis tended to be higher in those without liver metastasis. But gene expression in metastatic tumors of the liver was not always higher than in the primary tumors. The VEGF gene expression in the primary tumors with lymph node metastasis tended to be higher than in those without lymph node metastasis. Both VEGF and MMP-9 mRNA expression in the metastatic lymph nodes tended to be higher than in the primary tumors. Immunohistochemical staining for metastatic liver tumors showed that the expression of VEFG or MMP-2 protein was not observed in the cancer cells but in hepatocytes neighboring the metastatic nodules. These results suggest that the expression of VEGF or MMPs may be changed by the circumstances of target organs, and that cancer metastasis may be brough into being through an interrelationship among cancer, cells, stromal cells and hepatocytes.

Key words
colorectal cancer, vascular endothelial growth factor, matrix metallo-proteinases

Reprint requests
Shun-ichi Ishigami Otsu Red Cross Hospital
1-1-35 Nagara, Otss city, 520-0046, JAPAN

Accepted
December 3, 1997

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