Project/Area Number |
21590813
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Hiroshima University |
Principal Investigator |
KITADAI Yasuhiko 広島大学, 大学院・医歯薬学総合研究科, 准教授 (10304437)
|
Co-Investigator(Renkei-kenkyūsha) |
SHINAGAWA Kei 広島大学, 病院, 医科診療医 (50623609)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | 下部消化管学(小腸、大腸) / 骨髄由来間葉系幹細胞 / 間質 / 癌転移 / 分子標的治療 / MSC / CAF / 大腸癌 / Mesenchymal stem cell (MSC) / Carcinoma-associated fibroblast (CAF) / Colon cancer / Metastasis |
Research Abstract |
In an orthotopic nude mice model of colon cancer, mesenchymal stem cells(MSCs) traveled to tumor stroma, where they differentiated into carcinoma-associated fibroblast(CAF)-like cells. The KM12SM+ MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor-bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+ MSC xenograft, and survival in the mixed-cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow-derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.
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