C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA

Takayoshi Kaida, Hidetoshi Nitta, Yuki Kitano, Kensuke Yamamura, Kota Arima, Daisuke Izumi, Takaaki Higashi, Junji Kurashige, Katsunori Imai, Hiromitsu Hayashi, Masaaki Iwatsuki, Takatsugu Ishimoto, Daisuke Hashimoto, Yoichi Yamashita, Akira Chikamoto, Takahisa Imamura, Takatoshi Ishiko, Toru Beppu, Hideo Baba

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: Anaphylatoxin C5α is a strong chemoattractant of the complement system that binds the C5α receptor (C5αR). The expression of C5αR is associated with poor prognosis in several cancers. However, the role of C5αR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5αR on GC cell motility and invasion. Experimental Design: The mechanism of invasion via C5αR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5α treatment. Moreover, we investigated the relationship between C5αR expression and the prognosis of GC patients. Results: Two human GC cell lines (MKN1 and MKN7) had high C5αR expression. An invasion assay revealed that C5α stimulation promoted the invasive ability of MKN1 and MKN7 cells and that this was suppressed by knockdown of C5αR using siRNA or a C5αR-antagonist. Moreover, overexpression of C5αR in GC cells enhanced the conversion of RhoA-guanosine diphosphate (RhoA-GDP) to RhoA-guanosine triphosphate (RhoA-GTP) after C5α 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 C5αR 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 C5αR expression was 58.2% and 88.5%, respectively (p=0.008). Conclusions: This study is the first to demonstrate that C5αR 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.

Original languageEnglish
Pages (from-to)84798-84809
Number of pages12
JournalOncotarget
Volume7
Issue number51
DOIs
Publication statusPublished - Jan 1 2016

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Stomach Neoplasms
Anaphylatoxins
Stress Fibers
Pseudopodia
Guanosine
Diphosphates
Chemotactic Factors
Guanosine Triphosphate
Small Interfering RNA
Cell Movement
Blood Vessels
Neoplasms
Research Design
Biomarkers
Cell Line
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Kaida, T., Nitta, H., Kitano, Y., Yamamura, K., Arima, K., Izumi, D., ... Baba, H. (2016). C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA. Oncotarget, 7(51), 84798-84809. https://doi.org/10.18632/oncotarget.12656

C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA. / Kaida, Takayoshi; Nitta, Hidetoshi; Kitano, Yuki; Yamamura, Kensuke; Arima, Kota; Izumi, Daisuke; Higashi, Takaaki; Kurashige, Junji; Imai, Katsunori; Hayashi, Hiromitsu; Iwatsuki, Masaaki; Ishimoto, Takatsugu; Hashimoto, Daisuke; Yamashita, Yoichi; Chikamoto, Akira; Imamura, Takahisa; Ishiko, Takatoshi; Beppu, Toru; Baba, Hideo.

In: Oncotarget, Vol. 7, No. 51, 01.01.2016, p. 84798-84809.

Research output: Contribution to journalArticle

Kaida, T, Nitta, H, Kitano, Y, Yamamura, K, Arima, K, Izumi, D, Higashi, T, Kurashige, J, Imai, K, Hayashi, H, Iwatsuki, M, Ishimoto, T, Hashimoto, D, Yamashita, Y, Chikamoto, A, Imamura, T, Ishiko, T, Beppu, T & Baba, H 2016, 'C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA', Oncotarget, vol. 7, no. 51, pp. 84798-84809. https://doi.org/10.18632/oncotarget.12656
Kaida T, Nitta H, Kitano Y, Yamamura K, Arima K, Izumi D et al. C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA. Oncotarget. 2016 Jan 1;7(51):84798-84809. https://doi.org/10.18632/oncotarget.12656
Kaida, Takayoshi ; Nitta, Hidetoshi ; Kitano, Yuki ; Yamamura, Kensuke ; Arima, Kota ; Izumi, Daisuke ; Higashi, Takaaki ; Kurashige, Junji ; Imai, Katsunori ; Hayashi, Hiromitsu ; Iwatsuki, Masaaki ; Ishimoto, Takatsugu ; Hashimoto, Daisuke ; Yamashita, Yoichi ; Chikamoto, Akira ; Imamura, Takahisa ; Ishiko, Takatoshi ; Beppu, Toru ; Baba, Hideo. / C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA. In: Oncotarget. 2016 ; Vol. 7, No. 51. pp. 84798-84809.
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abstract = "Purpose: Anaphylatoxin C5α is a strong chemoattractant of the complement system that binds the C5α receptor (C5αR). The expression of C5αR is associated with poor prognosis in several cancers. However, the role of C5αR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5αR on GC cell motility and invasion. Experimental Design: The mechanism of invasion via C5αR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5α treatment. Moreover, we investigated the relationship between C5αR expression and the prognosis of GC patients. Results: Two human GC cell lines (MKN1 and MKN7) had high C5αR expression. An invasion assay revealed that C5α stimulation promoted the invasive ability of MKN1 and MKN7 cells and that this was suppressed by knockdown of C5αR using siRNA or a C5αR-antagonist. Moreover, overexpression of C5αR in GC cells enhanced the conversion of RhoA-guanosine diphosphate (RhoA-GDP) to RhoA-guanosine triphosphate (RhoA-GTP) after C5α 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 C5αR 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 C5αR expression was 58.2{\%} and 88.5{\%}, respectively (p=0.008). Conclusions: This study is the first to demonstrate that C5αR 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.",
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T1 - C5α receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA

AU - Kaida, Takayoshi

AU - Nitta, Hidetoshi

AU - Kitano, Yuki

AU - Yamamura, Kensuke

AU - Arima, Kota

AU - Izumi, Daisuke

AU - Higashi, Takaaki

AU - Kurashige, Junji

AU - Imai, Katsunori

AU - Hayashi, Hiromitsu

AU - Iwatsuki, Masaaki

AU - Ishimoto, Takatsugu

AU - Hashimoto, Daisuke

AU - Yamashita, Yoichi

AU - Chikamoto, Akira

AU - Imamura, Takahisa

AU - Ishiko, Takatoshi

AU - Beppu, Toru

AU - Baba, Hideo

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Purpose: Anaphylatoxin C5α is a strong chemoattractant of the complement system that binds the C5α receptor (C5αR). The expression of C5αR is associated with poor prognosis in several cancers. However, the role of C5αR in gastric cancer (GC) is unknown. The aim of this study was to examine the role of C5αR on GC cell motility and invasion. Experimental Design: The mechanism of invasion via C5αR was assessed by analyzing cytoskeletal rearrangement and RhoA activity after C5α treatment. Moreover, we investigated the relationship between C5αR expression and the prognosis of GC patients. Results: Two human GC cell lines (MKN1 and MKN7) had high C5αR expression. An invasion assay revealed that C5α stimulation promoted the invasive ability of MKN1 and MKN7 cells and that this was suppressed by knockdown of C5αR using siRNA or a C5αR-antagonist. Moreover, overexpression of C5αR in GC cells enhanced the conversion of RhoA-guanosine diphosphate (RhoA-GDP) to RhoA-guanosine triphosphate (RhoA-GTP) after C5α 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 C5αR 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 C5αR expression was 58.2% and 88.5%, respectively (p=0.008). Conclusions: This study is the first to demonstrate that C5αR 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.

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