| Project/Area Number |
24659185
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
ISHII Genichiro 独立行政法人国立がん研究センター, 臨床開発センター, ユニット長 (00270869)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | がん関連線維芽細胞 / 分子標的 / がん微小環境 / がん組織 / がんの進展、転移 / がん間質細胞の分子標的治療法 |
|---|
| Research Abstract |
Cancer associated fibroblasts (CAFs) reportedly influence tumor progression via the secretion of extracellular matrix proteins, proteases, cytokines, and growth factors. Recently, the significance of CAFs was reported to be associated with resistance to molecular-targeted therapy.
This study shows lung adenocarcinoma cell lines harboring EGFR activating mutation became more resistant to EGFRTKI when cocultured with PDPN expressing CAFs, compared with control CAFs in vitro. Furthermore, 105 postoperative recurrent patients with PDPN positive CAFs had a significantly lower EGFRTKIs response, compared with those with PDPN negative CAFs. Our studies show PDPN positive CAFs plays an important role in primary resistance to EGFRTKIs and may be an ideal therapeutic target for use in combination therapy with EGFRTKIs.
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