Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/90942
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
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 1532-1827 |
Statement of Responsibility: | 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 |
Published version: | http://dx.doi.org/10.1038/bjc.2014.232 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.