Analysis of cleavage fragments produced by proteolysis on cancer cell membrane

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: KOSHIKAWA NAOHIKO 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 部長 (70334282)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 膵癌 / プロセシング / MT1-MMP / HB-EGF / EphA2

Outline of Final Research Achievements

An early detection method for pancreatic cancer has not been established so far. In this study, we focused on the proteolytic fragment of substrates of membrane-type-1 matrix metalloprotease (MT1-MMP), which is important for the malignant progression of pancreatic. In this study, we made monoclonal antibodies to the proteolytic fragments of MT1-MMP substrates, heparin-binding EGF-like growth factor, HB-EGF and EphA2, and established quantitative ELISA assays for the fragments. As the results, the detection sensitivity of the HB-EGF fragment was not sufficient and required further improvement. In contrast, the serum levels of EphA2 fragment in the patient with pancreatic cancer including an early stage was a significantly higher than that of healthy donors. These results suggest that the EphA2 fragment could be a new biomarker for early pancreatic cancer diagnosis.

Free Research Field

腫瘍診断学

Academic Significance and Societal Importance of the Research Achievements

膵癌は早期診断、早期治療以外に完治を見込めない難治癌である。しかし、現状では早期膵癌を見出すバイオマーカーはない。今回着目したMT1-MMP、EphA2は共に早期の膵癌で高発現していることが報告されていることから、それら相互作用としての蛋白分解で生じる基質断片は早期の膵癌の存在を示す重要なバイオマーカーになる可能性をもつ。今後、多検体血清を用いた臨床研究により、これら分解断片の早期膵癌のバオマーカーとしての有用性を明らかとすることが必要となる。