Pathological study on metalloproteinases in tissue remodeling under pathological conditions

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249022
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: OKADA Yasunori 慶應義塾大学, 医学部, 教授 (00115221)
• Co-Investigator(Kenkyū-buntansha): MOCHIZUKI Satsuki 慶應義塾大学, 医学部, 専任講師 (80365428) ; FUJII Yutaka 福井大学, 医学部, 教授 (80211522) ; SHIMODA Masayuki 慶應義塾大学, 医学部, 専任講師 (70383734) ; KIMURA Tokuhiro 慶應義塾大学, 医学部, 助教 (40445200)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: MMP / ADAM / TIMP / 組織リモデリング / 悪性腫瘍 / 急性大動脈解離 / 変形性関節症 / 関節軟骨

Outline of Final Research Achievements

We have studied the roles of metalloproteinases in pathological tissue remodeling, and obtained the following data: 1) ADAM28 produced by lung carcinoma cells plays a key role in cancer cell proliferation and metastasis and this molecule seems to be a good drug target for the treatment of non-small cell lung cancers. 2) Activities of metalloproteinases derived from cancer-associated fibroblasts control cancer cell proliferation, invasion and metastasis. 3) Neutrophil-derived MMP-9 has an important role in the initiation of acute aortic dissection, which is an extremely intractable disease with poor prognosis. 4) The activity of ADAMTS4, which is a major metalloproteinase implicated for aggrecan degradation in human osteoarthritis (a major cause of locomotive syndrome), is inhibited by CCN1(Cyr61) and KIAA1199 is a key enzyme for hyaluronan depolymerization.

Free Research Field

病理学