2010 Fiscal Year Final Research Report
Essential role of Cadherin family in esophageal cancer and Potential for a novel molecule of targeted therapy
| Project/Area Number |
21870026
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Cell biology
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| Research Institution | Okayama University |
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Principal Investigator |
NOMA Kazuhiro Okayama University, 医療教育統合開発センター, 助教 (10534761)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 食道癌 / N-cadherin / Barrett食道癌 / 分子標的治療 / Tumor microenvironment |
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| Research Abstract |
In this research, our purpose is the analysis of cadherin family in esophageal carcinogenesis and to clarify the relation of N-cadherin and tumor microenvironment. In addition, a new molecular target therapy was aimed as a completely new approach by inhibiting the action of N-cad. First, we confirmed that 3/10 cases in Barrett's cancer expressed N-cad, especially strong expression in leading edge of tumor invasion. In esophageal cancer cell lines, TE4 and 10 expressed N-cad. Stimulation of collagen I, and TGF on those cells lead to over-express N-cad, in the other side, no change in cells which originally not expressed N-cad. However, stimulated cells showed morphological changes, suggesting EMT may have been induced. We also investigated relation of iron control and EMT through cadherins, based on the previous reports. We confirmed the antitumor effect of that in vivo and vitro. In vivo, we used iron deficient diet and, in vitro used iron chelator. In iron deficient conditions, N-cad expression was decreased in vitro, and the cells showed decreased those migration and invasion ability, suggesting that the possibility that N-cad is an important molecule in cancer invasion and tumor growth. Now we used siRNA-N-cad and reduced expression in cancer cells and would confirm the same phenomenon in esophageal cancer cells. As the future, we scheduled to consider a new multidisciplinary cancer therapy using N-cad inhibitors.
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