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Influence of the C5a–C5a receptor system on breast cancer progression and patient prognosis

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Abstract

Background

Emerging evidence has shown activation of the complement system in cancer tissues and anaphylatoxin C5a release from C5 by cancer cells, suggesting C5a as a component in the cancer microenvironment. We revealed aberrant expression of C5a receptor (C5aR) in various human cancers and C5a-elicited enhancement of C5aR-expressing cancer cell invasion.

Methods

To explore an influence of the C5a–C5aR system in breast cancer (BC), we investigated BC C5aR expression in relation to clinicopathological parameters of the patients and an effect of C5a on BC cell proliferation.

Results

BC cell C5aR expression was observed immunohistochemically in 22 of 171 patients (13 %) and related to larger tumor size, higher nuclear grade and Ki-67 labeling index, presence of lymph node metastasis and advanced clinical stages. Interestingly, BC cells were C5aR-negative in all patients with BC in situ and C5aR-positive rate was high (38 %) in patients with hormone receptor-negative, namely triple-negative BC. For BC cells in metastasized lymph nodes, 12 of 22 patients (55 %) were C5aR-positive and included 7 patients with C5aR-negative BC in the primary site. Survival rate of patients with C5aR-positive BC was lower than that of patients with C5aR-negative BC. C5a enhanced proliferation of C5aR-expressing triple-negative BC cells in a C5aR-dependent manner.

Conclusion

Relation of BC C5aR expression to tumor development and poor prognosis of the patients and proliferation enhancing effect of C5a on C5aR-expressing BC cells suggest that the C5a–C5aR system is closely associated with BC progression. This system may be a new target to treat BC patients, particularly with triple-negative BC.

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Abbreviations

BC:

Breast cancer

C5:

The fifth complement component

C5aR:

C5a-receptor

TNBC:

Triple-negative breast cancer

RFS:

Relapse-free survival

DRFS:

Distant relapse-free survival

BCSS:

Breast cancer-specific survival

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Acknowledgments

We thank Miss. Chisato Takagi, Yuki Teramoto, and Chihiro Murakami, Shokei University, Kumamoto, for their technical assistance. This work was supported in part by Japanese Science Progress Society KAKENHI Grants 22590363 and 25460498 to Takahisa Imamura and 25461982 to Toru Kariu.

Author information

Authors and Affiliations

  1. Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Takahisa Imamura & Tatsuko Kubo

  2. Department of Breast and Endocrine Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Mutsuko Yamamoto-Ibusuki, Aiko Sueta & Hirotaka Iwase

  3. Department of Immunogenetics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Atsushi Irie

  4. Medical Quality Management Center, Kumamoto University Hospital, Kumamoto, Japan

    Ken Kikuchi

  5. Shokei University, Kumamoto, Japan

    Toru Kariu

Authors
  1. Takahisa Imamura
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  2. Mutsuko Yamamoto-Ibusuki
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  3. Aiko Sueta
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  4. Tatsuko Kubo
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Correspondence to Takahisa Imamura.

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Imamura, T., Yamamoto-Ibusuki, M., Sueta, A. et al. Influence of the C5a–C5a receptor system on breast cancer progression and patient prognosis. Breast Cancer 23, 876–885 (2016). https://doi.org/10.1007/s12282-015-0654-3

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  • DOI: https://doi.org/10.1007/s12282-015-0654-3

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