Mechanism of Metastasis of Gastric Cancer, from the Viewpoit of Basement Membrane Degradative Enzyme

Keiichi Yoshino¹⁾, Kiyoshi Kubochi⁴⁾, Isao Okazaki²⁾, Yoshihide Otani⁵⁾, Shigeo Matsuyama³⁾, Humio Suzuki⁶⁾, Tatsu Fukase¹⁾, Kenichiro Aizawa¹⁾, Hideo Matsui¹⁾, Atsushi Shimada¹⁾, Kyuya Ishibiki¹⁾, Osahiko Abe¹⁾

¹⁾Department of Surgery, ²⁾Department of Preventive Medicine and Public Health, Keio University School of Medicine, ³⁾Central Research Lab, National Defence Medical College, ⁴⁾Department of Surgery, National Tokyo Second Hospital, ⁵⁾Department of Surgery, Urawa City Hospital, ⁶⁾Department of Surgery, Federation of National Public Service and Faciliated Personnel Mutual Aid Association, Tachikawa Hospital

The activity of basement membrane degradative enzyme (type IV collagen degradative enzyme, IV ase) in cancer tissue may be indicative of the degree of biological malignancy of the cancer, since the basement membrane encircling the primary cancer site and vessels is cleaved in the process of cancer metastasis, especially when cancer cells are released from their primary site and invade adjacent connective tissue, undergoing both intravasation and extravasation after lodgement. The IV ase activity of gastric cancer tissue was measured by means of the solution assay developed by us, and the results were as follows; the activity was found to be higher in the advancing front of the cancer, to be higher in cases with marked microscopic vascular invasion and in cases with widely disseminated lymph node metastasis. In addition, the concentration of urinary 3-hydroxyproline (3-HYP), which is derived mainly from type IV collagen, was measured, with the results showing that it was higher in cases of advanced gastric cancer than in healthy subjects and cases of early gastric cancer. The following conclusion appears justified: the basement membrane and IV ase participate in cancer metastasis. Our findings suggest that the measurement of IV ase activity in cancer tissue might contribute to choosing powerful strategies against the cancer and that 3-HYP based cancer screening might be possible.

Key words
cancer metastasis, basement membrane, collagen degradative enzyme

Reprint requests
Keiichi Yoshino Department of Surgery, Keio University School of Medicine
35 Shinanomachi, Shinjuku-ku, Tokyo, 160 JAPAN

Accepted
December 12, 1990

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