Investigation of cancer promotion by a cancer microenvironment factor C5a and establishment of the therapy targeting the C5a-C5a receptor system.

2016 Fiscal Year Final Research Report

• Project/Area Number: 25460498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kumamoto University
• Principal Investigator: IMAMURA TAKAHISA 熊本大学, 大学院生命科学研究部(医), 准教授 (20176499)
• Co-Investigator(Renkei-kenkyūsha): IRIE ATSUSHI 熊本大学, 生命科学研究部, 講師 (30250343)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: C5a / 癌 / 浸潤 / 増殖 / 転移 / プロテアーゼ / 阻害剤 / 受容体拮抗剤

Outline of Final Research Achievements

Anaphylatoxin C5a receptor (C5aR) was expressed in cancer cells from all organs examined and at various rates in organs. Several cancer cell lines also expressed C5aR. C5a augmented C5aR-expressing cancer cell invasion in a MMP-6 dependent manner in Matrigel chambers and in implanted nude mouse skin. C5a also enhanced cancer cell lung metastasis in a C5aR-dependent manner. By cell membrane-bound furin-like serine protease cancer cells generated C5a from C5, even it in plasma, augmenting their invasiveness. These C5a effects on cancer cells were inhibited by antibodies against either C5a or C5aR, and by a C5aR antagonist. These results indicate presence of a cancer cell autoactivation pathway via C5a generation and suggest availability of a new cancer therapy targeting the C5a-C5aR axis or the cancer protease.

Free Research Field

医歯薬学