2013 Fiscal Year Final Research Report
Novel target therapy for the HGF/cMET axis and HB-EGF in gastric cancer
| Project/Area Number |
23591921
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
YASUMOTO Kazuo 金沢大学, がん進展制御研究所, 准教授 (90262592)
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| Co-Investigator(Renkei-kenkyūsha) |
YANO Seiji 金沢大学, がん進展制御研究所, 教授 (30294672)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 胃癌 / がん性腹膜炎 / HGF/MET axis / 分子標的治療 |
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| Research Abstract |
Scirrhous gastric cancer frequently develops into peritoneal carcinomatosis with malignant ascites. We investigated the role of the HGF/MET axis in peritoneal carcinomatosis in scirrhous cancer. Scirrhous cell lines produced peritoneal carcinomatosis with massive ascites after intraperitoneal injection in nude mice. Their proliferation was stimulated by exogenous HGF in vitro. MET-TKIs inhibited HGF-stimulated proliferation of scirrhous cells. Furthermore, MET-TKIs prolonged the survival of mice bearing established tumors by scirrhous cells. In clinical specimens, HGF was markedly produced by stromal fibroblasts in scirrous cancer. Our results strongly suggest that paracrine HGF-induced activation of MET-mediated signaling pathways plays an important role in the pathogenesis of peritoneal carcinomatosis in scirrhous gastric cancer.Thus, MET signaling pathway may be a potential therapeutic target for peritoneal carcinomatosis of gastric cancer, even without MET amplification.
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