The role of inflammatory biomarker OLMF4 to the malignancy of inflammatory bowel disease related tumors

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07026
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kitasato University
• Principal Investigator: Yoshida Tsutomu 北里大学, 医学部, 教授 (90316943)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 炎症性腸疾患 / 潰瘍性大腸炎 / 悪性腫瘍 / Olfactomedin-4 / OLFM4

Outline of Final Research Achievements

To elucidate the poorer differentiation and prognosis of inflammatory bowel disease related tumor, we analyzed the association of biomarker OLMF4. OLFM4 binds frizzled-7, which would lead the suppression of WNT/beta-catenin pathway. OLMF4 was secreted in exosome, and exosomal OLMF4 inhibited the expression of activated form of beta-catenin and EMT markers. Expression of OLMF4 in inflammatory foci of UC-related tumors was reduce along with the tumorigenesis, which suggests the relationship with the malignancy of tumors. It is possible that suppression of EMT by OLMF4 secreted in exosome would be the cause of the malignant potential of IBD related tumor.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎及びクローン病は若年発症の難病炎症性腸疾患(IBD)で、患者数は増加している。長期罹患により悪性腫瘍を多発発症すると共に、通常型大腸癌に比して低分化で悪性度が高いことが知られているが、その機序は明らかになっていない。今回の研究成果は、申請者がこれまでに明らかにしてきたIBD特異的バイオマーカーであるOLFM4(olfactomedin-4)が、IBD関連腫瘍の高悪性度特性に関わっていることを明らかにするもので、特にexosome型分泌が関与することを明らかにしたことは学術的にも新機軸である。