Role of proteoglycans in diseases: Regulation of cell behavior and maintenance of tissue structure

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293096
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Aichi Medical University
• Principal Investigator: WATANABE Hideto 愛知医科大学, 付置研究所, 教授 (90240514)
• Co-Investigator(Renkei-kenkyūsha): SUGIURA Nobuo 愛知医科大学, 分子医科学研究所, 准教授 (90454420) ; NAGAI Naoko 愛知医科大学, 分子医科学研究所, 助教 (00367799) ; TSUCHIMOTO Jun 愛知医科大学, 分子医科学研究所, 助教 (70632868)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: プロテオグリカン / バーシカン / 遺伝子改変マウス / 創傷治癒 / がん微小環境

Outline of Final Research Achievements

Versican (Vcan) is a large chondroitin sulfate proteoglycan in the extracellular matrix (ECM). Here, we report that Vcan inhibits tumor growth. Local depletion of stromal Vcan expression in Vcan<flox/flox> mice by infecting cre-expressing adenoviruses facilitates growth of QRsP11 fibrosarcoma cells, which is observed as early as day 7, followed by tumor angiogenesis as early as day 14. Loss of local Vcan decreases tumor stroma including fibroblasts and dense collagen fibers, and alters localization of TGFbeta;. These results demonstrate that stromal Vcan inhibits tumor growth by maintaining the ECM structure and TGFbeta-signaling. We also analyzed Vcan<delta3/delta3> embryos, whose Vcan lacks the A subdomain of the G1 domain and exhibits less hyaluronan-binding activity, and found that Vcan plays an important role in formation of dermis. These results clearly demonstrate that Vcan contributes to ECM formation.

Free Research Field

分子病理学