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Type: Journal article
Title: Exogenous administration of protease-resistant, non-matrix-binding IGFBP-2 inhibits tumour growth in a murine model of breast cancer
Author: Soh, C.
McNeil, K.
Owczarek, C.
Hardy, M.
Fabri, L.
Pearse, M.
Delaine, C.
Forbes, B.
Citation: British Journal of Cancer, 2014; 110(12):2855-2864
Publisher: Nature Publishing Group
Issue Date: 2014
ISSN: 0007-0920
Statement of
C-L Soh, K McNeil, C M Owczarek, M P Hardy, L J Fabri, M Pearse, C A Delaine and B E Forbes
Abstract: BACKGROUND: Insulin-like growth factors (IGF-I and IGF-II) signal via the type 1 IGF receptor (IGF-1R) and IGF-II also activates the insulin receptor isoform A (IR-A). Signalling via both receptors promotes tumour growth, survival and metastasis. In some instances IGF-II action via the IR-A also promotes resistance to anti-IGF-1R inhibitors. This study assessed the efficacy of two novel modified IGF-binding protein-2 (IGFBP-2) proteins that were designed to sequester both IGFs. The two modified IGFBP-2 proteins were either protease resistant alone or also lacked the ability to bind extracellular matrix (ECM). METHODS: The modified IGFBP-2 proteins were tested in vitro for their abilities to inhibit cancer cell proliferation and in vivo to inhibit MCF-7 breast tumour xenograft growth. RESULTS: Both mutants retained low nanomolar affinity for IGF-I and IGF-II (0.8-2.1-fold lower than IGFBP-2) and inhibited cancer cell proliferation in vitro. However, the combined protease resistant, non-matrix-binding mutant was more effective in inhibiting MCF-7 tumour xenograft growth and led to inhibition of angiogenesis. CONCLUSIONS: By removing protease cleavage and matrix-binding sites, modified IGFBP-2 was effective in inhibiting tumour growth and reducing tumour angiogenesis.
Keywords: Insulin-like growth factor; IGFBP; xenograft; breast cancer; vascularisation
Rights: © 2014 Cancer Research UK. All rights reserved
DOI: 10.1038/bjc.2014.232
Appears in Collections:Aurora harvest 2
Molecular and Biomedical Science publications

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