The Metabolism of Extracellular Matrix and Gastric Cancer Invasion and Metastasis -Comparison between Scirrhous Type and Non-scirrhous Type-

Kiyoshi Kubochi, Atsushi Shimada, Hideo Matsui, Yoh Isobe, Shingo Shima, Shinji Ogawa¹⁾, Keiichi Yoshino¹⁾, Kyuya Ishibiki²⁾, Masaki Kitajima³⁾

Department of Surgery, Institute of Clinical Research, National Second Tokyo Hospital
¹⁾Department of Surgery, Ichikawa General Hospital, Tokyo Dental College
²⁾Department of Surgery, National Saitama Hospital
³⁾Department of Surgery, School of Medicine, Keio University

To investigate the role of collagens in gastric cancer tissues with regard to cancer invasion and metastasis. We homogenized cancer tissues and measured the collagenolytic activity against type I and IV collagens in tissue homogenates. We also studied the location of a tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer tissues by the immunoperoxidase staining procedure and measured the serum levels of TIMP-1 in patients before the operation for gastric cancer. We compared these results in scirrhous and non-scirrhous types of gastric cancer. Collagenolytic activities against both type I and IV collagens in the non-scirrhous type were significantly higher than those in the scirrhous type (p<0.01). TIMP-1 was stained on collagens in cancer tissues and therefore a large amount of TIMP-1 was present in the scirrhous type. The serum level of TIMP-1 in undifferentiated cancer was high (p<0.05), especially in the scirrhous type (p<0.025). These results suggest that gastric cancer cells forming the scirrhous type might have the ability to accumulate collagens in cancer tissue and that cancer cells should use the dynamic biological activity of the extracellular matrix and then invade the stomach wall. Because the TIMP level in the scirrhous type was higher in cancer tissue snd serum of patients than in the nonscirrhous type, the mechanism of cancer cell metastasis in the scirrhous type characterizing lymph node metastasis and peritoneal dissemination might be different from those in the non-scirrhous type characterizing venous metastasis mainly.

Key words
scirrhous type of gastric cancer, metalloproteinase and tissue inhibitor of metalloproteinasis, cancer invasion and metastasis of gastric cancer

Reprint requests
Kiyoshi Kubochi Department of Surgery, National Second Tokyo Hospital
2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-0021 JAPAN

Accepted
December 3, 1997

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