Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88)

Hidetoshi Nitta, Yoshihiro Wada, Yoshiaki Kawano, Yoji Murakami, Atsushi Irie, Keisuke Taniguchi, Ken Kikuchi, Gen Yamada, Kentaro Suzuki, Jiro Honda, Masayo Wilson-Morifuji, Norie Araki, Masatoshi Eto, Hideo Baba, Takahisa Imamura

研究成果: ジャーナルへの寄稿記事

44 引用 (Scopus)

抄録

Purpose: The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. We therefore sought C5aR expression and a direct influence of the C5a-C5aR axis on cancer cells. Experimental Design: C5aR expression was investigated in human cancer tissues and cell lines. Effects of C5a stimulation on cancer cells were studied by cytoskeletal rearrangement, time-lapse analysis, Matrigel chamber assay, and invasion in nude mouse in a comparison of C5aR-expressing cancer cells with control cells. Results: C5aR was aberrantly expressed in various human cancers. Several cancer cell lines also expressed C5aR. C5a triggered cytoskeletal rearrangement and enhanced cell motility three-fold and invasiveness 13-fold of C5aR-expressing cancer cells. Such enhancement by C5a was not observed in control cells. Cancer cell invasion was still enhanced in the absence of C5a concentration gradient and even after the removal of C5a stimulation, suggesting that random cell locomotion plays an important role in C5a-triggered cancer cell invasion. C5a increased the release of matrix metalloproteinases (MMP) from cancer cells by two- to 11-fold, and inhibition of MMP activity abolished the C5a-enhancing effect on cancer cell invasion. Compared with control cells, C5aR-expressing cells spread 1.8-fold more broadly at implanted nude mouse skin sites only when stimulated with C5a. Conclusions: These results illustrate a novel activity of the C5a-C5aR axis that promotes cancer cell invasion through motility activation and MMP release. Targeting this signaling pathway may provide a useful therapeutic option for cancer treatment.

元の言語英語
ページ(範囲)2004-2013
ページ数10
ジャーナルClinical Cancer Research
19
発行部数8
DOI
出版物ステータス出版済み - 4 15 2013

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Anaphylatoxin C5a Receptor
Anaphylatoxins
Cell Movement
Neoplasms
Matrix Metalloproteinases
Nude Mice
Cell Line
Tumor Microenvironment
Chemotactic Factors

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88). / Nitta, Hidetoshi; Wada, Yoshihiro; Kawano, Yoshiaki; Murakami, Yoji; Irie, Atsushi; Taniguchi, Keisuke; Kikuchi, Ken; Yamada, Gen; Suzuki, Kentaro; Honda, Jiro; Wilson-Morifuji, Masayo; Araki, Norie; Eto, Masatoshi; Baba, Hideo; Imamura, Takahisa.

:: Clinical Cancer Research, 巻 19, 番号 8, 15.04.2013, p. 2004-2013.

研究成果: ジャーナルへの寄稿記事

Nitta, H, Wada, Y, Kawano, Y, Murakami, Y, Irie, A, Taniguchi, K, Kikuchi, K, Yamada, G, Suzuki, K, Honda, J, Wilson-Morifuji, M, Araki, N, Eto, M, Baba, H & Imamura, T 2013, 'Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88)', Clinical Cancer Research, 巻. 19, 番号 8, pp. 2004-2013. https://doi.org/10.1158/1078-0432.CCR-12-1204
Nitta, Hidetoshi ; Wada, Yoshihiro ; Kawano, Yoshiaki ; Murakami, Yoji ; Irie, Atsushi ; Taniguchi, Keisuke ; Kikuchi, Ken ; Yamada, Gen ; Suzuki, Kentaro ; Honda, Jiro ; Wilson-Morifuji, Masayo ; Araki, Norie ; Eto, Masatoshi ; Baba, Hideo ; Imamura, Takahisa. / Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88). :: Clinical Cancer Research. 2013 ; 巻 19, 番号 8. pp. 2004-2013.
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title = "Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88)",
abstract = "Purpose: The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. We therefore sought C5aR expression and a direct influence of the C5a-C5aR axis on cancer cells. Experimental Design: C5aR expression was investigated in human cancer tissues and cell lines. Effects of C5a stimulation on cancer cells were studied by cytoskeletal rearrangement, time-lapse analysis, Matrigel chamber assay, and invasion in nude mouse in a comparison of C5aR-expressing cancer cells with control cells. Results: C5aR was aberrantly expressed in various human cancers. Several cancer cell lines also expressed C5aR. C5a triggered cytoskeletal rearrangement and enhanced cell motility three-fold and invasiveness 13-fold of C5aR-expressing cancer cells. Such enhancement by C5a was not observed in control cells. Cancer cell invasion was still enhanced in the absence of C5a concentration gradient and even after the removal of C5a stimulation, suggesting that random cell locomotion plays an important role in C5a-triggered cancer cell invasion. C5a increased the release of matrix metalloproteinases (MMP) from cancer cells by two- to 11-fold, and inhibition of MMP activity abolished the C5a-enhancing effect on cancer cell invasion. Compared with control cells, C5aR-expressing cells spread 1.8-fold more broadly at implanted nude mouse skin sites only when stimulated with C5a. Conclusions: These results illustrate a novel activity of the C5a-C5aR axis that promotes cancer cell invasion through motility activation and MMP release. Targeting this signaling pathway may provide a useful therapeutic option for cancer treatment.",
author = "Hidetoshi Nitta and Yoshihiro Wada and Yoshiaki Kawano and Yoji Murakami and Atsushi Irie and Keisuke Taniguchi and Ken Kikuchi and Gen Yamada and Kentaro Suzuki and Jiro Honda and Masayo Wilson-Morifuji and Norie Araki and Masatoshi Eto and Hideo Baba and Takahisa Imamura",
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T1 - Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88)

AU - Nitta, Hidetoshi

AU - Wada, Yoshihiro

AU - Kawano, Yoshiaki

AU - Murakami, Yoji

AU - Irie, Atsushi

AU - Taniguchi, Keisuke

AU - Kikuchi, Ken

AU - Yamada, Gen

AU - Suzuki, Kentaro

AU - Honda, Jiro

AU - Wilson-Morifuji, Masayo

AU - Araki, Norie

AU - Eto, Masatoshi

AU - Baba, Hideo

AU - Imamura, Takahisa

PY - 2013/4/15

Y1 - 2013/4/15

N2 - Purpose: The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. We therefore sought C5aR expression and a direct influence of the C5a-C5aR axis on cancer cells. Experimental Design: C5aR expression was investigated in human cancer tissues and cell lines. Effects of C5a stimulation on cancer cells were studied by cytoskeletal rearrangement, time-lapse analysis, Matrigel chamber assay, and invasion in nude mouse in a comparison of C5aR-expressing cancer cells with control cells. Results: C5aR was aberrantly expressed in various human cancers. Several cancer cell lines also expressed C5aR. C5a triggered cytoskeletal rearrangement and enhanced cell motility three-fold and invasiveness 13-fold of C5aR-expressing cancer cells. Such enhancement by C5a was not observed in control cells. Cancer cell invasion was still enhanced in the absence of C5a concentration gradient and even after the removal of C5a stimulation, suggesting that random cell locomotion plays an important role in C5a-triggered cancer cell invasion. C5a increased the release of matrix metalloproteinases (MMP) from cancer cells by two- to 11-fold, and inhibition of MMP activity abolished the C5a-enhancing effect on cancer cell invasion. Compared with control cells, C5aR-expressing cells spread 1.8-fold more broadly at implanted nude mouse skin sites only when stimulated with C5a. Conclusions: These results illustrate a novel activity of the C5a-C5aR axis that promotes cancer cell invasion through motility activation and MMP release. Targeting this signaling pathway may provide a useful therapeutic option for cancer treatment.

AB - Purpose: The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. We therefore sought C5aR expression and a direct influence of the C5a-C5aR axis on cancer cells. Experimental Design: C5aR expression was investigated in human cancer tissues and cell lines. Effects of C5a stimulation on cancer cells were studied by cytoskeletal rearrangement, time-lapse analysis, Matrigel chamber assay, and invasion in nude mouse in a comparison of C5aR-expressing cancer cells with control cells. Results: C5aR was aberrantly expressed in various human cancers. Several cancer cell lines also expressed C5aR. C5a triggered cytoskeletal rearrangement and enhanced cell motility three-fold and invasiveness 13-fold of C5aR-expressing cancer cells. Such enhancement by C5a was not observed in control cells. Cancer cell invasion was still enhanced in the absence of C5a concentration gradient and even after the removal of C5a stimulation, suggesting that random cell locomotion plays an important role in C5a-triggered cancer cell invasion. C5a increased the release of matrix metalloproteinases (MMP) from cancer cells by two- to 11-fold, and inhibition of MMP activity abolished the C5a-enhancing effect on cancer cell invasion. Compared with control cells, C5aR-expressing cells spread 1.8-fold more broadly at implanted nude mouse skin sites only when stimulated with C5a. Conclusions: These results illustrate a novel activity of the C5a-C5aR axis that promotes cancer cell invasion through motility activation and MMP release. Targeting this signaling pathway may provide a useful therapeutic option for cancer treatment.

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