| Project/Area Number |
22791270
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 消化器癌 / 抗血管新生 / 耐性機構 / 消火器癌 / 癌微小環境 / 低酸素 |
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| Research Abstract |
We transplanted solid tumors derived from human colon carcinoma into the cecum wall of nude mice and treated them with anti-VEGF antibody or normal control IgG. Despite decreased microvessel density in the tumors with anti-VEGF treatment, tumor growth was incompletely impaired. Microarray analysis revealed 97 genes that were predominantly expressed in tumors treated with anti-VEGF antibody compared with untreated tumors. Among them, we further focused on stanniocalcin 2(STC2) which has been reported to be regulated by hypoxia inducible factor-1(HIF-1) under hypoxic condition and to induce epithelial mesenchymal transition. Gene Set Enrichment Analysis(GSEA) showed the activation of transforming growth factorβ(TGFβ) pathway in tumors treated with anti-VEGF antibody. These findings suggest that hypoxic conditions due to VEGF inhibition may induce EMT and stemness of transplanted tumors, resulting in enhanced invasive and metastatic potential. Immunohistochemistry of HIF-1αand HIF-2αrevealed that HIF-1αprotein was more likely to locate in the nucleus of tumors treated with anti-VEGF antibody compared with untreatedtumors. Immunohistochemistry of colon cancer stem cell markers, CD133, CD44 and ALDH1 revealed that expression levels of ALDH1 were higher in tumors treated with anti-VEGF antibody than those in tumors treated with control IgG.
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