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10.3892/ol.2017.6555

http://scihub22266oqcxt.onion/10.3892/ol.2017.6555
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suck abstract from ncbi


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pmid28928834
      Oncol+Lett 2017 ; 14 (3 ): 2961-2969
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  • CD55 and CD59 expression protects HER2-overexpressing breast cancer cells from trastuzumab-induced complement-dependent cytotoxicity #MMPMID28928834
  • Wang Y ; Yang YJ ; Wang Z ; Liao J ; Liu M ; Zhong XR ; Zheng H ; Wang YP
  • Oncol Lett 2017[Sep]; 14 (3 ): 2961-2969 PMID28928834 show ga
  • 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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