Type

Journal Article

Authors

J Crown
M J Duffy
F O'Sullivan
P M McGowan
N O'Donovan
D M Collins

Subjects

Microbiology

Topics
drug effects genetics cell line tumor breast neoplasms receptor erbb 2 cell proliferation male killer cells natural antibodies monoclonal humanized trastuzumab antineoplastic agents humans adult middle aged metabolism gene amplification pharmacology erbb2 protein human antibody dependent cell cytotoxicity female immunology

Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines. (2011)

Abstract Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by CD56+natural killer (NK) cells may contribute to the activity of trastuzumab in HER-2-amplified tumours. In this study, we investigated the possibility that trastuzumab might induce ADCC against HER-2-non-amplified breast cancer cells. Induction of NK cell-mediated ADCC was examined in trastuzumab-treated HER-2-non-amplified breast cancer cell lines. HER-2 protein levels were also determined in tumour and autologous normal tissue samples from patients with HER-2 negative breast cancer. Trastuzumab induced a significant ADCC response in the HER-2-amplified HCC1954 and SKBR3 cell lines, and in all five of the non-amplified cell lines, which had low levels of detectable HER-2 by western blot (CAL-51, CAMA-1, MCF-7, T47D, and EFM19). Trastuzumab did not induce ADCC in the K562 control cell line or MDA-MB-468, which has very low levels of HER-2 detectable by enzyme-linked immunosorbent assay (ELISA) only. HER-2 protein was detected by ELISA in 14/15 patient tumour samples classified as HER-2-non-amplified. Significantly lower levels of HER-2 were detected in normal autologous tissue compared with tumour samples from the same patients. Our results suggest that HER-2-non-amplified breast cancer cells, with low but detectable levels of HER-2 protein, can bind trastuzumab and initiate ADCC.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

J Crown, M J Duffy, F O'Sullivan, P M McGowan, N O'Donovan, D M Collins

Experts in our system

1
John Crown
Dublin City University
Total Publications: 104
 
2
Michael J Duffy
University College Dublin
 
3
Finbarr O'Sullivan
Dublin City University
Total Publications: 24
 
4
Patricia M McGowan
Dublin City University
Total Publications: 8
 
5
Norma O'Donovan
Dublin City University
Total Publications: 59
 
6
Denis M Collins
Dublin City University
Total Publications: 26