2010 Fiscal Year Final Research Report
Development of molecular target therapy for gastric cancer targeted for the CXCR4/CXCL12 axis and HB-EGF
| Project/Area Number |
20591565
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 Kanazawa University, 附属病院, 講師 (90262592)
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| Co-Investigator(Renkei-kenkyūsha) |
YANO Seiji 金沢大学, がん研究所, 教授 (30294672)
MINAMOTO Toshinari 金沢大学, がん研究所, 教授 (50239323)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 胃十二指腸外科学 |
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| Research Abstract |
In this study, we showed that the EGFR ligands, amphiregulin and HB-EGF, are abundant in malignant ascites. Amphiregulin strongly enhanced the proliferation of CXCR4-expressing human gastric cancer NUGC4 cells, whereas HB-EGF markedly induced migration of fibroblasts. Moreover, HB-EGF and CXCL12 together enhanced TNF□-converting enzyme (TACE)-dependent amphiregulin shedding from functional CXCR4-expressing NUGC4 cells. Cetuximab, an anti-EGFR monoclonal antibody, effectively reduced tumor growth and ascites formation, and therefore dramatically prolonged survival in nude mice inoculated with NUGC4 cells. Our findings provide a novel insight into treatments that target tumor cells and their microenvironments during the development of peritoneal carcinomatosis from gastric cancer (Clin Cancer Res 2011 in press).
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