Molecular mechanism of MMP-7-enhanced liver metastasis of colon cancer, and its application for liver regenerative medicine

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K12900
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Yokohama City University
• Principal Investigator: Higashi Shouichi 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (10275076)
• Co-Investigator(Renkei-kenkyūsha): KIMURA YAYOI 横浜市立大学, 先端医科学研究センター, 准教授 (80391936)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: MMP-7 / HAI-1 / がん転移 / 細胞間接着 / 細胞凝集 / コレステロール硫酸 / 細胞表層プロテオリシス

Outline of Final Research Achievements

(1) We found that hepatocyte growth factor activator inhibitor type 1 (HAI-1), a membrane-bound Kunitz-type serine protease inhibitor, is an MMP-7 substrate; MMP-7 cleaves HAI-1 at the membrane-proximal region, and releases the extracellular region as soluble HAI-1(sHAI-1).
(2) The released sHAI-1, but not the membrane-bound HAI-1, has an ability to induce cancer cell aggregation, and the HAI-1 region corresponding to amino acids 141-249 is essential for the cell aggregation-inducing activity.
(3) A cell-surface cholesterol sulfate-independent proteolytic action of MMP-7 is critical for the sHAI-1-mediated induction of cell aggregation, whereas cholesterol sulfate is needed for the MMP-7-catalyzed generation of sHAI-1.

Free Research Field

生体医工学・生体材料学