Dataset Information

C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA.

ABSTRACT:

Purpose

Anaphylatoxin C5a is a strong chemoattractant of the complement system that binds the C5a receptor (C5aR). The expression of C5aR is associated with poor prognosis in several cancers. However, the role of C5aR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5aR on GC cell motility and invasion.

Experimental design

The mechanism of invasion via C5aR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5a treatment. Moreover, we investigated the relationship between C5aR expression and the prognosis of GC patients.

Results

Two human GC cell lines (MKN1 and MKN7) had high C5aR expression. An invasion assay revealed that C5a stimulation promoted the invasive ability of MKN1 and MKN7 cells and that this was suppressed by knockdown of C5aR using siRNA or a C5aR-antagonist. Moreover, overexpression of C5aR in GC cells enhanced the conversion of RhoA-guanosine diphosphate (RhoA-GDP) to RhoA-guanosine triphosphate (RhoA-GTP) after C5a stimulation and caused morphological changes, including increased expression of stress fibers and filopodia. Examination of tumor specimens from 100 patients with GC revealed that high C5aR expression (35 of 100 samples, 35.0%) was associated with increased invasion depth, vascular invasion and advanced stage. The 5-year overall survival of patients with high or low C5aR expression was 58.2% and 68.5%, respectively (p=0.008).

Conclusions

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.

SUBMITTER: Kaida T

PROVIDER: S-EPMC5356699 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA.

Kaida Takayoshi T Nitta Hidetoshi H Kitano Yuki Y Yamamura Kensuke K Arima Kota K Izumi Daisuke D Higashi Takaaki T Kurashige Junji J Imai Katsunori K Hayashi Hiromitsu H Iwatsuki Masaaki M Ishimoto Takatsugu T Hashimoto Daisuke D Yamashita Yoichi Y Chikamoto Akira A Imanura Takahisa T Ishiko Takatoshi T Beppu Toru T Baba Hideo H

Oncotarget 20161201 51

<h4>Purpose</h4>Anaphylatoxin C5a is a strong chemoattractant of the complement system that binds the C5a receptor (C5aR). The expression of C5aR is associated with poor prognosis in several cancers. However, the role of C5aR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5aR on GC cell motility and invasion.<h4>Experimental design</h4>The mechanism of invasion via C5aR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5a treatmen ...[more]

PMID: 27756879

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Project description:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative dementia characterized by the decline of cognition and the presence of neuropathological changes including neuronal loss, neurofibrillary pathology and extracellular senile plaques. A neuroinflammatory process is also triggered and complement activation has been hypothesized to have a relevant role in this local inflammatory response. C5a, a proinflammatory anaphylatoxin generated after complement activation, exerts its chemotactic and inflammatory functions through the CD88 receptor while the more recently discovered C5L2 receptor has been postulated to have an anti-inflammatory role. Previously, we reported that a CD88 specific antagonist (PMX205) decreased the pathology and improved cognition in transgenic models of AD suggesting that C5a/C5aR interaction has an important role in the progression of the disease. METHODS:The present study characterizes the expression of the two receptors for C5a in human brain with confirmed post mortem diagnosis of vascular dementia (VD) or AD as well as age matched controls by immunohistochemistry and Western blot analysis using several antibodies against different epitopes of the human receptors. RESULTS:The CD88 and C5L2 antibodies revealed increased expression of both receptors in AD samples as compared to age-matched controls or VD brain tissue by Western blot and immunohistochemistry, using multiple antibodies and distinct cohorts of brain tissue. Immunostaining showed that both the C5L2 and CD88 antibodies similarly labeled abundant neurofibrillary tangles, neuropil threads and dystrophic neurites associated with plaques in the hippocampus and frontal cortex of AD cases. In contrast, little or no neuronal staining, tangles or dystrophic neurites associated with plaques were observed in control or VD brains. CD88 and C5L2 receptors are associated with both early (AT8) and mature (PHF1) neurofibrillary tangles and can be found either independently or colocalized with each other. CONCLUSIONS:The observed association of CD88 and C5L2 with neurofibrillary pathology suggests a common altered pathway of degradation.

Dataset Information

C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA.

Purpose

Experimental design

Results

Conclusions

Publications

C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA.

Similar Datasets

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