Analysis for the effect of C5a receptor on cancer cell and development for targeted therapeutic strategy to C5a receptor

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: NITTA Hidetoshi 熊本大学, 医学部附属病院, 非常勤診療医師 (90555749)
• Co-Investigator(Kenkyū-buntansha): BABA Hideo 熊本大学, 大学院生命科学研究部, 教授 (20240905) ; NAKAHARA Osamu 熊本大学, 医学部附属病院, 非常勤診療医師 (40583042) ; BEPPU Toru 熊本大学, 医学部附属病院, 特任教授 (70301372) ; TAKAMAORI Hiroshi 熊本大学, 医学部附属病院, 非常勤診療医師 (90363514)
• Research Collaborator: KAIDA Takayoshi 熊本大学, 大学院生命科学研究部, 大学院生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 補体C5a / C5a受容体 / 胃癌浸潤・転移

Outline of Final Research Achievements

We examined the effect of C5a receptor (C5aR) on Gastric cancer (GC). Two human GC cell lines had high C5aR expression. An invasion assay revealed that C5a stimulation promoted the invasive ability of them. Moreover, overexpression of C5aR in GC cells enhanced the conversion of RhoA-GDP to RhoA-GTP after C5a stimulation and caused morphological changes, including increased expression of stress fibers and filopodia. Examination of tumor specimens from patients with GC revealed that high C5aR expression was associated with increased invasion depth, vascular invasion and advanced stage. The 5-year overall survival of patients with high C5aR expression was significantly worse than that of patients with low expression. This study is the first to demonstrate that C5aR promotes GC cell invasion by activating RhoA and is associated with a poor prognosis in GC patients. Therefore, this study provides a biomarker for GC patients who require an advanced therapeutic strategy.

Free Research Field

消化器外科学