消化器癌のリンパ行性転移を促進する腫瘍微小環境の解明とその制御

促进胃肠癌淋巴转移的肿瘤微环境的阐明和控制

• 批准号: 22591526
• 负责人: 蔵原 弘
• 金额: $ 2.83万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591526/
• 关键词: リンパ行性転移; 腫瘍微小環境; リンパ管新生; リンパ管新生因子; EMT; MET; TAM

本研究は,消化器癌のリンパ行性転移を促進するメカニズムの解明を目的としたものである.近年,癌の転移に影響を与える因子としてEpithelial-mesenchymal transition (EMT)および腫瘍微小環境におけるマクロファージ(tumor-associated macrophage : TAM)の働きが注目されている.われわれは,膵癌症例においてZEB1およびZEB2の発現がEMTを引き起こし,更にリンパ節転移を促進することを明らかにした.一方,転移リンパ節においてはmesenchymal-epithelial transition (MET)が転移巣の増大を促進している可能性があることを示した.次に,多様な性質を有するマクロファージのうち,免疫抑制方向に分化したM2-TAMが転移形成前にリンパ節に到達し,リンパ管新生を引き起こすことでリンパ節転移を促進している可能性があることを示した.更に,folate receptor β (FRβ)陽性マクロファージは血管新生を引き起こし,血行性転移を促進することを明らかにした.FRβ陽性マクロファージとリンパ行性転移との関連は今後の研究課題である.上記研究により,腫瘍のEMTとMETはリンパ行性転移において非常に重要な役割を有することを明らかにした.また,主病巣の腫瘍微小環境のみならず,リンパ節の微小環境においてもTAMは重要な役割を有し,転移を促進することを明らかにした.転移抑制治療開発に向けて,更に研究を続ける必要がある.

In this study, digestive tract cancer was induced to increase the incidence of cancer in digestive organs. In recent years, cancer metastasis has been affected by many factors, such as Epithelial-mesenchymal transition (EMT), microenvironment, environmental impact, and environmental impact. (tumor-associated macrophage:) has paid close attention to the development of cancer. There are many cases of cancer, such as cancer, ZEB1, ZEB2, EMT, EMT, cancer, cancer and cancer. On one side, you can move the mesenchymal-epithelial transition (MET) to promote the possibility. In the second stage, there are multiple symptoms, the direction of immunosuppression is differentiation (M2-TAM), the direction of immunosuppression is differentiation (differentiation), and the direction of immunosuppression is differentiation (differentiation). Before the formation of the disease, the tube freshman is introduced to promote the possibility of infection. In addition, folate receptor β (FR β) induces angiogenesis, and hematopoietic transfer promotes the development of angiogenesis. Fr β induces rapid angiogenesis, and FR β induces further research in the future. In the last part of the study, you can find out that it is very important to EMT the MET to make sure that the service is very important. The main disease is that the micro-environment is affected, the micro-environment is affected, and's important service is cut, and the transfer is needed to promote the improvement of the environment. The treatment of migration inhibition should be carried out, and the necessary treatment should be studied.

项目成果

Expression of BMP-7 in human gastric cancer and its clinical significance.

• DOI: 10.1038/sj.bjc.6606075
• 发表时间: 2011-02-15
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Prognostic impact of CD133 expression in gastric carcinoma.

• 发表时间: 2010-06
• 期刊: Anticancer research
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• 作者: S. Ishigami;S. Ueno;T. Arigami;Y. Uchikado;T. Setoyama;Hideo Arima;Y. Kita;H. Kurahara;H. Okumura;M. Matsumoto;Y. Kijima;S. Natsugoe

Clinical Significance of Folate Receptor β-expressing Tumor-associated Macrophages in Pancreatic Cancer

• DOI: 10.1245/s10434-012-2263-0
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Prognostic impact of CD168 expression in gastric cancer.

• DOI: 10.1186/1471-2407-11-106
• 发表时间: 2011-03-24
• 期刊: BMC cancer
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• 作者: Ishigami S;Ueno S;Nishizono Y;Matsumoto M;Kurahara H;Arigami T;Uchikado Y;Setoyama T;Arima H;Yoshiaki K;Kijima Y;Kitazono M;Natsugoe S
• 通讯作者: Natsugoe S

Significance of Lymphangiogenesis in Primary Tumor and Draining Lymph Nodes During Lymphatic Metastasis of Pancreatic Head Cancer

• DOI: 10.1002/jso.21744
• 发表时间: 2010-12-01
• 期刊: JOURNAL OF SURGICAL ONCOLOGY
• 影响因子: 2.5
• 作者: Kurahara, Hiroshi;Takao, Sonshin;Natsugoe, Shoji
• 通讯作者: Natsugoe, Shoji