2021 Fiscal Year Final Research Report
Investigation of the potential candidate gene in cancer cell invasion using cancer cell lines and 3-D in vitro model
Project/Area Number |
19K09284
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55040:Respiratory surgery-related
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Research Institution | Kobe University |
Principal Investigator |
Doi Takefumi 神戸大学, 医学部附属病院, 助教 (70814490)
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Co-Investigator(Kenkyū-buntansha) |
眞庭 謙昌 神戸大学, 医学研究科, 教授 (50362778)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | BEX1 / 肺腺癌 / 悪性胸膜中皮腫 / 浸潤能 / 細胞増殖能 / DL-CGH |
Outline of Final Research Achievements |
Invasion has a significant role in cancer progression and metastasis. Previously, we assessed the invasive ability of cancer cells using an easy to prepare double layered collagen gel hemisphere (DL-CGH) method by which cancer cell invasion can be easily visualized. The present study examined multiple lung adenocarcinoma and malignant pleural mesothelioma (MPM) cell lines using the DL-CGH method and identified inherently invasive cell lines. Next, by comparing gene expression between invasive and noninvasive cells by cDNA microarray, the potential candidate gene brain-expressed x-linked protein 1 (Bex1) was identified to be involved in cancer invasion, as it was highly expressed in the invasive cell lines. Downregulation of Bex1 suppressed the invasion and proliferation of the invasive tumor cell lines. The findings of the present study suggested that Bex1 may promote metastasis in vivo and could be a potential oncogene and molecular therapeutic target in lung adenocarcinoma and MPM.
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Free Research Field |
呼吸器外科学分野
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Academic Significance and Societal Importance of the Research Achievements |
癌が浸潤・転移する際には多段階のプロセスを経ることが知られており、我々が開発した浸潤能評価のための2層化コラーゲンゲル半球法は、特に癌が周囲組織・間質へ浸潤する様子を観察・評価するのに優れていた。今回用いた肺腺癌・悪性胸膜中皮腫細胞株が周囲組織に浸潤する際、外に向かって樹状突起を伸ばして浸潤する様子が見られ、BEX1を抑制することで樹状突起が形成されず浸潤ができなくなることが観察できた。この結果、BEX1は癌が樹状突起を伸ばして周囲に浸潤するのに深く関与し、浸潤のメカニズムに関わる有用な遺伝子であると考えられる。BEX1の働きを抑制する薬剤の開発は新たな分子標的薬の開発につながる可能性がある。
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