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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.