Journal Article


M J Duffy
J Crown
G Murphy
C J Tape
L Flanagan
N O'Donovan
N Synnott
A Murray
M Mullooly
P M McGowan
and 1 others



pharmacology humans molecular targeted therapy apoptosis genetics immunology signal transduction drug effects cell line tumor tumor necrosis factor alpha convertase disease progression antagonists inhibitors cell proliferation drug therapy antibodies monoclonal humanized triple negative breast neoplasms adam proteins pathology cell movement

Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells. (2015)

Abstract Identification and validation of a targeted therapy for triple-negative breast cancer (TNBC), that is, breast cancers negative for oestrogen receptors, progesterone receptors and HER2 amplification, is currently one of the most urgent problems in breast cancer treatment. EGFR is one of the best-validated driver genes for TNBC. EGFR is normally activated following the release of ligands such as TGFα, mediated by the two MMP-like proteases ADAM (a disintegrin and metalloproteinase)-10 and ADAM-17. The aim of this study was to investigate the antitumour effects of a monoclonal antibody against ADAM-17 on an in vitro model of TNBC. We investigated an inhibitory cross-domain humanised monoclonal antibody targeting both the catalytic domain and the cysteine-rich domain of ADAM17-D1(A12) in the HCC1937 and HCC1143 cell lines. D1(A12) was found to significantly inhibit the release of TGFα, and to decrease downstream EGFR-dependent cell signalling. D1(A12) treatment reduced proliferation in two-dimensional clonogenic assays, as well as growth in three-dimensional culture. Furthermore, D1(A12) reduced invasion of HCC1937 cells and decreased migration of HCC1143 cells. Finally, D1(A12) enhanced cell death in HCC1143 cells. Our in vitro findings suggest that targeting ADAM-17 with D1(A12) may have anticancer activity in TNBC cells.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

M J Duffy, J Crown, G Murphy, C J Tape, L Flanagan, N O'Donovan, N Synnott, A Murray, M Mullooly, P M McGowan and 1 others

Experts in our system

Michael J Duffy
University College Dublin
John Crown
Dublin City University
Total Publications: 104
Norma O'Donovan
Dublin City University
Total Publications: 59
Naoise C Synnott
Dublin City University
Alyson Murray
Dublin City University
Total Publications: 6
Patricia M McGowan
Dublin City University
Total Publications: 8