2013 Fiscal Year Final Research Report
COX-2 blockade immunologically suppresses brain metastasis of lung cancer
| Project/Area Number |
24700998
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor immunology
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| Research Institution | Kinki University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
YOSHIE Osamu 近畿大学, 医学部, 教授 (10166910)
NAKATA Susumu 愛知県がんセンター, 研究所, 主任研究員 (80590695)
OKUDA Takeshi 近畿大学, 医学部, 講師 (10340796)
KATO Amami 近畿大学, 医学部, 教授 (00233776)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 肺がん / 転移性脳腫瘍 / 非ステロイド系抗炎症薬 / 免疫抑制性細胞 |
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| Research Abstract |
Associations between the regular use of NSAIDs and reduced cancer risks in human have been shonw. NSAIDs function as COX-2 inhibitors that prevent the production of PGE2, which induces MDSCs in cancer-bearing hosts. We thus hypothesized that COX-2 blockade would suppress brain metastasis of cancers by inhibiting MDSC development and their chemokine-mediated accumulation in the tumor microenvironment (TME). In both mouse and human brain metastasis cases, the expression levels of COX-2 and CCL2, a chemokine primarily attracting MDSCs, were increased in the tumor tissues compared with the periphery or normal brain. Concomitantly, the infiltration of MDSCs was observed at high levels in the tumor tissues. In the mouse brain tumor models using LL/2 murine lung cancer cell line, treatment with NSAIDs inhibited brain metastasis formation with the suppression of MDSCs. Our findings show that the COX-2 pathway promotes brain metastases of lung cancers by development and accumulation of MDSCs.
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