2021 Fiscal Year Final Research Report

Biological role of metadherin in liver metastases of colon cancer and development of novel molecular target therapy

Research Project

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Project/Area Number	19K09134
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Teikyo University
Principal Investigator	Shimizu Hiroaki 帝京大学, 医学部, 教授 (80272318)
Co-Investigator(Kenkyū-buntansha)	幸田圭史帝京大学, 医学部, 教授 (50260477) 山崎一人帝京大学, 医学部, 教授 (60302519) 小杉千弘帝京大学, 医学部, 講師 (60375681) 細川勇帝京大学, 医学部, 助教 (60623676) 首藤潔彦帝京大学, 医学部, 准教授 (90372359) 野島広之帝京大学, 医学部, 講師 (10507320) 村上崇帝京大学, 医学部, 助教 (80621870)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	大腸癌 / 肝転移 / メタドヘリン / Snail1 / 上皮間葉転換
Outline of Final Research Achievements	Metadherin（MTDH） and Snail1 are known to be key molecules in epithelial-mesenchymal transition(EMT) and an important process in cancer metastasis. To investigate clinical significance of EMT markers in colorectal cancer (CRC), especially relation between the expression of MTDH and Snail1 in CRC/liver metastasis and clinical outcome. Surgically resected specimens were investigated the expression of MTDH and Snail1 by immunohistochemical staining. Results: MTDH was strongly expressed in the liver metastasis, as compared to the primary CRC.Expression of Snail1 in the primary CRC with liver metastasis was significantly increased, as compared to CRC without liver metastasis. Furthermore, high Snail1 expression in liver metastases was associated with poor prognosis. These results suggest that EMT may strongly contribute to the mechanism of liver metastasis from primary CRC. Furthermore, high Snail1 expression in liver metastasis may be a significant prognostic factor after hepatectomy.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	本研究では大腸癌の原発巣、肝転移巣を一連の実験系で検討し、肝転移メカニズムを考察することを主眼とする。転移浸潤過程でのMTDH/Snail1の転移制御機構における役割が明らかとなれば、それに応じた intervention による治療戦略の可能性も考えられる。つまり、MIDH、Snail1 をターゲットとした治療を確立することで現行の化学療法とは異なった視点から、肝転移再発の抑制に対しての治療が考えられる。また、癌の浸潤転移のメカニズムに重要な上皮間葉転換（EMT）は、癌の転移に関する普遍的な分子機構の謎を解く上で非常に有用であり、今後の新しい癌治療への展開の可能性切り開くものと考える。