Development of novel therapeutics and multidisciplinary strategies for colorectal cancer based on epithelial-to-mesenchymal transition

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10660
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: Miura Koh 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (40282074)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 上皮間葉転換 / 大腸癌

Outline of Final Research Achievements

To further promote our research (Sasaki H, et al. Cancer Sci. 2008 Apr;99(4):7 11-9.; Matsuda Y, et al. Cancer Sci. 2016 May;107(5):619-28.) and to develop novel therapeutics for refractory colorectal cancer through functional analyses of genes regulating epithelial-to-mesenchymal transition (EMT), we performed functional analyses of the EMT-associated genes such as Serpini1 and CHST11. With Western blotting, we clarified that SERPINI1 protein in supernatants suppressed the expression of E-cadherin in colorectal cancer cells with EMT phenotype such as SW620. The same results were found in COLO320 as well. On the other hand, similar results were not found in colorectal cancer cells such as HT-29, SW948, T84, LoVo, HCT8, HCT15, and DLD-1. This analysis is also ongoing on CHST11. We also analyzed immunohistochemical staining of SERPINI1 and CHST11 in orthotopic mice models of human colorectal cancer cells.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

大腸癌を含む上皮系悪性腫瘍は、本来の上皮細胞が形質転換することで発生しますが、その過程で間葉系細胞の特性を獲得してくることがあり（上皮間葉転換；epithelial-to-mesenchymal transition: EMT）、癌がさらに浸潤、転移する機能を獲得して癌治療を困難にすることが知られています。私たちはこれまでの先行研究において、大腸癌におけるEMT関連遺伝子を明らかにし、解析を続けてきました。難治性の大腸癌そのほかの悪性腫瘍の新しい治療につなげることを目的として、この研究を続けています。