Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0050098
Title: ARTEMIN Promotes De Novo Angiogenesis in ER Negative Mammary Carcinoma through Activation of TWIST1-VEGF-A Signalling
Authors: Banerjee, A.
Wu, Z.-S.
Qian, P.-X.
Kang, J.
Liu, D.-X.
Zhu, T.
Lobie, P.E. 
Issue Date: 21-Nov-2012
Citation: Banerjee, A., Wu, Z.-S., Qian, P.-X., Kang, J., Liu, D.-X., Zhu, T., Lobie, P.E. (2012-11-21). ARTEMIN Promotes De Novo Angiogenesis in ER Negative Mammary Carcinoma through Activation of TWIST1-VEGF-A Signalling. PLoS ONE 7 (11) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0050098
Abstract: The neurotrophic factor ARTEMIN (ARTN) has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC). Human microvascular endothelial cells (HMEC-1) do not express ARTN but respond to exogenously added, and paracrine ARTN secreted by ER-MC cells. ARTN promoted endothelial cell proliferation, migration, invasion and 3D matrigel tube formation. Angiogenic behaviour promoted by ARTN secreted by ER-MC cells was mediated by AKT with resultant increased TWIST1 and subsequently VEGF-A expression. In a patient cohort of ER-MC, ARTN positively correlated with VEGF-A expression as measured by Spearman's rank correlation analysis. In xenograft experiments, ER-MC cells with forced expression of ARTN produced tumors with increased VEGF-A expression and increased microvessel density (CD31 and CD34) compared to tumors formed by control cells. Functional inhibition of ARTN by siRNA decreased the angiogenic effects of ER-MC cells. Bevacizumab (a humanized monoclonal anti-VEGF-A antibody) partially inhibited the ARTN mediated angiogenic effects of ER-MC cells and combined inhibition of ARTN and VEGF-A by the same resulted in further significant decrease in the angiogenic effects of ER-MC cells. Thus, ARTN stimulates de novo tumor angiogenesis mediated in part by VEGF-A. ARTN therefore co-ordinately regulates multiple aspects of tumor growth and metastasis. © 2012 Banerjee et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/109191
ISSN: 19326203
DOI: 10.1371/journal.pone.0050098
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