In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4146-4146
Abstract:
Background: C5a is one of the important factors produced on complement pathway and a strong chemokine. There is emerging evidence that C5a is generated in the cancer microenvironment and C5a receptor (C5aR) is expressed in various cancer cells and associated with invasive ability in several cancer cells. However, the role of C5aR in gastric cancer (GC) is still mostly unknown. Aim: To investigate the clinical significance of C5aR expression in human GC. Method: 168 patients underwent gastrectomy after the diagnosis of gastric cancer from January 1st 2001 to December 31th 2009. C5aR-expression of GC cells was investigated in all 168 patients and was analyzed in regard to an association with clinicopathological factors and outcomes in the patients. Additionally, in vitro experiments were used to examine the proliferation and invasion of GC cells by using the GC cell lines that had high-expression of C5aR. Result: High-expression of C5aR was found in 55 patients (32.7%). High-expression of C5aR was significantly related to depth of invasion, stage, lymphatic and vascular invasion. Among the 146 patients with a tumor stage lower than stageIV, the 5-years recurrence-free and overall survival rates of patients in the high-expression of C5aR group were significantly lower than those in the low-expression of C5aR group (91.0% vs 52.4%, p = 0.007 and 87.2% vs 59.1%, p = 0.003, respectively). The high-expression of C5aR group had more frequently distant metastasis than the low-expression of C5aR group during the follow-up time, presenting itself mainly in liver metastasis and peritoneal dissemination (p = 0.020 and p = 0.026). We found that the gastric cancer cell lines MKN1 and MKN7 had the high-expression of C5aR with western blotting in vitro. Moreover, matrigel chamber assay revealed that 10 nM of recombinant C5a enhances cell invasiveness of MKN1 by 2.55-fold and the cell invasiveness of MKN7 by 2.90-fold, but such an enhancement by C5a was not observed in control cells. Conclusions: The gastric cancer patients with a high expression of C5aR were associated with poor prognosis, and the invasive ability of gastric cancer cell lines highly expressing of C5aR were promoted by C5a. Thus, targeting this C5a-C5aR axis might provide a useful therapeutic option for gastric cancer treatment. Citation Format: Takayoshi Kaida, Hidetoshi Nitta, Kota Arima, Hideaki Takeyama, Takaaki Higashi, Katunobu Taki, Hiromitsu Hayashi, Daisuke Hashimoto, Akira Chikamoto, Takatoshi Ishiko, Toru Beppu, Hideo Baba. Overexpression of C5a receptor becomes risk factor in gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4146. doi:10.1158/1538-7445.AM2015-4146
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-4146
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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