2007 Fiscal Year Final Research Report Summary
The study of immunosuppressive mechanisms induced by gastrointestinal cancer during epithelial-mesnchymal transition and clinical application of this target therapy
| Project/Area Number |
18591484
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
SAKURAI Toshiharu Keio University, School of Medicine, Instructor (20101933)
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| Co-Investigator(Kenkyū-buntansha) |
KUDO Chie Keio University, School of Medicine, Instructor (90424126)
TSUKAMOTO Nobuo Keio University, School of Medicine, Instructor (20407117)
KAWAKAMI Yutaka Keio University, School of Medicine, Professor (50161287)
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| Project Period (FY) |
2006 – 2007
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| Keywords | epithelial-mesenchymal transition / gastroenterogic cancer / Snail / immunosuppression |
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| Research Abstract |
Epithelial-mesenchymal transition (EMT) is thought to be a key step toward metastases, and the molecular mechanisms have been investigated from aspects of cancer cells. However the interaction between host immunity and the tumor cells during EMT has not been clarified yet In this study, we first established human pancreatic cancer cell line Panc-1 cells with typical EMT features such as decreased adhesion and increased invasion by transduction with snail gene, which is one of the essential transcription factor governing EMT. lb analyze how the snail transfectants would affect immune responses, we then cultured human PBMCs with the snail transfectants. In the culture with snail transfectants, immunosuppressive cells such as impaired CD11c^+ cells and CD4^+FoxP3^+ cells were increased as compared with the culture with the mock transfectant We further conducted GeneChip array analysis to compare gene expression between the snail transfectant and the parental cells, and identified the specific mediators involved in the snail-induced immunosuppressive mechanisms. The mAbs specific for the molecules significantly inhibited both induction of immunosuppression and tumor invasion. These data demonstrate that snail^+ tumor cells during EMT simultaneously induce immunosuppressive microenvironment, leading to acceleration of tumor metastasis. Blockade of the EMT-related molecules would be effective in simultaneously suppressing tumor metastasis and immunosuppression, both which are still critical issues in cancer therapy. This strategy could be promising to improve anti-tumor efficacies induced by various therapies for patients with cancers.
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