2014 Fiscal Year Final Research Report
Analysis of malignant progression of cancer cells affected by the tumor microenvironment
| Project Area | Integrative Research on Cancer Microenvironment Network |
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| Project/Area Number |
22112005
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2010-04-01 – 2015-03-31
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| Keywords | 癌 / がん幹細胞 / 血管 / ストロマ細胞 |
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| Outline of Final Research Achievements |
In terms of malignant transformation in cancer cells, interaction of cancer stem cells with endothelial cells or myofibroblasts as tumor microenvironmental cells was analyzed. As a result, when tumor vasculature was focused, we found that cancer stem cells existing near myofibroblasts abundantly localizing at perivascular area show drug resistance. To assess this phenomenon, we established tumor myofibroblasts cell line and analyzed the up-regulating genes in myofibroblasts upon exposure with hypoxia and/or serum starvation. In this treatment, we identified that CD44 is up-regulated under the hypoxia and this molecule supports stemness of cancer stem cells and induces drug resistance of cancer cells. In order to improve the tissue hypoxia in the tumor microenvironment, it is required to normalize very leaky and immature tumor vasculature. In this experiment, we found that apelin normalizes tumor vasculature, resulting in improvement of drug delivery and tumor immunity.
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| Free Research Field |
分子発生生物学
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