2018 Fiscal Year Final Research Report
Clarification of the mechanisms of cancer cell attachment and infiltration to suppress liver metastasis, and development of its prophylaxis.
| Project/Area Number |
16K10562
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
kondo tadashi 筑波大学, 医学医療系, 教授 (00375495)
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| Co-Investigator(Kenkyū-buntansha) |
田村 孝史 筑波大学, 医学医療系, 研究員 (20633192)
小川 光一 筑波大学, 医学医療系, 講師 (20733637)
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| Research Collaborator |
Matsumura Hideki
Takahashi Kazuhiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 肝転移 / 血小板 / 癌細胞 / 膠着 / 炎症性サイトカイン |
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| Outline of Final Research Achievements |
We clarified that platelets and cancer cells are located at the same place in the sinusoidal space. However, it was difficult to judge if this changes of the sinusoidal environment was secondary to platelet attachment to the sinusoid or the heat from the intravital microscope. In order to elucidate this mechanisms, we decided to use mass hepatectomized model, and assess the impact of platelets on parenchymal cell and non-parenchymal cells in the sinusoidal space. TNF-a and IL-6 levels in the liver, which are mainly released by liver sinusoidal epithelial cells and Kupffer cells, were found to increase under thrombocytotic condition after thrombopoetin administration, with activation of their downstream signals. Further, HGF level increased under thrombocytotic condition, which have anti-apoptotic effect on hepatocytes. Based on these results, we are planning to compare these effects after establishing liver metastasis model.
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| Free Research Field |
肝臓
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の目的は、癌転移の起こるメカニズムを癌細胞と肝に存在する肝細胞や非実質細胞との接着や浸潤の観点から解明することである。肝血管内で癌細胞が血小板に膠着していることを確認したが、癌転移モデルの確立が難しく、その理由を明らかにできなかった。そこで、血小板の血管内の環境に対する影響を解明する必要があると考え、よく使用される大量肝切除モデルで検討した。トロンボポエチンにより血小板が増加すると、肝非実質から分泌される炎症性サイトカインの発現が増加し、下流シグナルも活性化した。また、坑アポトーシス効果を示すHGFの発現も増加した。肝転移モデルを確立後に、本結果と比較検討を行う予定である。
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