Open Access

CD55 and CD59 expression protects HER2‑overexpressing breast cancer cells from trastuzumab‑induced complement‑dependent cytotoxicity

  • Authors:
    • Yu Wang
    • Ya‑Jun Yang
    • Zhu Wang
    • Juan Liao
    • Mei Liu
    • Xiao‑Rong Zhong
    • Hong Zheng
    • Yan‑Ping Wang
  • View Affiliations

  • Published online on: July 8, 2017     https://doi.org/10.3892/ol.2017.6555
  • Pages: 2961-2969
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A large proportion (40‑60%) of patients with human epidermal growth factor receptor 2 (HER2)‑overexpressing breast cancer do not benefit from trastuzumab treatment, potentially due to the lack of complement‑dependent cytotoxicity (CDC) activation. In the present study, the effect of complement decay‑accelerating factor (CD55) and CD59 glycoprotein precursor (CD59) expression on trastuzumab‑induced CDC in HER2‑positive breast cancer cell lines was investigated. The CD55 and CD59‑overexpressing and HER2‑positive cell lines SK‑BR‑3 and BT474 were selected for subsequent experiments. Blocking CD55 and CD59 function using targeting monoclonal antibodies significantly enhanced the cell lysis of SK‑BR‑3 and BT474 cells following treatment with trastuzumab. In addition, following treatment with 0.1 U/ml phosphatidylinositol‑specific phospholipase C (PI‑PLC) for 1 h, CD55 and CD59 surface expression was significantly decreased, and the cell lysis rate was further enhanced. Treatment of SK‑BR‑3 cells with short hairpin RNA (shRNA) targeting CD55 and CD59 downregulated CD55 and CD59 expression at the mRNA and protein levels, and resulted in significantly enhanced trastuzumab‑induced CDC‑dependent lysis. The data from the present study suggested that CD55 and CD59 serve roles in blocking trastuzumab‑induced CDC, therefore strategies targeting CD55 and CD59 may overcome breast cancer cell resistance to trastuzumab. The results from the present study may provide a basis for developing suitable, personalized treatment strategies to improve the clinical efficacy of trastuzumab for patients with HER2‑positive breast cancer.
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September-2017
Volume 14 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Wang Y, Yang YJ, Wang Z, Liao J, Liu M, Zhong XR, Zheng H and Wang YP: CD55 and CD59 expression protects HER2‑overexpressing breast cancer cells from trastuzumab‑induced complement‑dependent cytotoxicity. Oncol Lett 14: 2961-2969, 2017
APA
Wang, Y., Yang, Y., Wang, Z., Liao, J., Liu, M., Zhong, X. ... Wang, Y. (2017). CD55 and CD59 expression protects HER2‑overexpressing breast cancer cells from trastuzumab‑induced complement‑dependent cytotoxicity. Oncology Letters, 14, 2961-2969. https://doi.org/10.3892/ol.2017.6555
MLA
Wang, Y., Yang, Y., Wang, Z., Liao, J., Liu, M., Zhong, X., Zheng, H., Wang, Y."CD55 and CD59 expression protects HER2‑overexpressing breast cancer cells from trastuzumab‑induced complement‑dependent cytotoxicity". Oncology Letters 14.3 (2017): 2961-2969.
Chicago
Wang, Y., Yang, Y., Wang, Z., Liao, J., Liu, M., Zhong, X., Zheng, H., Wang, Y."CD55 and CD59 expression protects HER2‑overexpressing breast cancer cells from trastuzumab‑induced complement‑dependent cytotoxicity". Oncology Letters 14, no. 3 (2017): 2961-2969. https://doi.org/10.3892/ol.2017.6555