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https://hdl.handle.net/2440/90942
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dc.contributor.author | Soh, C. | - |
dc.contributor.author | McNeil, K. | - |
dc.contributor.author | Owczarek, C. | - |
dc.contributor.author | Hardy, M. | - |
dc.contributor.author | Fabri, L. | - |
dc.contributor.author | Pearse, M. | - |
dc.contributor.author | Delaine, C. | - |
dc.contributor.author | Forbes, B. | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | British Journal of Cancer, 2014; 110(12):2855-2864 | - |
dc.identifier.issn | 0007-0920 | - |
dc.identifier.issn | 1532-1827 | - |
dc.identifier.uri | http://hdl.handle.net/2440/90942 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | C-L Soh, K McNeil, C M Owczarek, M P Hardy, L J Fabri, M Pearse, C A Delaine and B E Forbes | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | © 2014 Cancer Research UK. All rights reserved | - |
dc.source.uri | http://dx.doi.org/10.1038/bjc.2014.232 | - |
dc.subject | Insulin-like growth factor; IGFBP; xenograft; breast cancer; vascularisation | - |
dc.title | Exogenous administration of protease-resistant, non-matrix-binding IGFBP-2 inhibits tumour growth in a murine model of breast cancer | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/bjc.2014.232 | - |
pubs.publication-status | Published | - |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
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