Lysyl oxidase plays a critical role in endothelial cell stimulation to drive tumor angiogenesis

Ann-Marie Baker, Demelza Bird, Jonathan C. Welti, Morgane Gourlaouen, Georgina Lang, Graeme I. Murray, Andrew R. Reynolds, Thomas R. Cox, Janine T. Erler

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70 Citations (Scopus)

Abstract

Identification of key molecules that drive angiogenesis is critical for the development of new modalities for the prevention of solid tumor progression. Using multiple models of colorectal cancer, we show that activity of the extracellular matrix–modifying enzyme lysyl oxidase (LOX) is essential for stimulating endothelial cells in vitro and angiogenesis in vivo. We show that LOX activates Akt through platelet-derived growth factor receptor ß (PDGFRß) stimulation, resulting in increased VEGF expression. LOX-driven angiogenesis can be abrogated through targeting LOX directly or using inhibitors of PDGFRß, Akt, and VEGF signaling. Furthermore, we show that LOX is clinically correlated with VEGF expression and blood vessel formation in 515 colorectal cancer patient samples. Finally, we validate our findings in a breast cancer model, showing the universality of these observations. Taken together, our findings have broad clinical and therapeutic implications for a wide variety of solid tumor types. Cancer Res; 73(2); 583–94. ©2012 AACR.
Original languageEnglish
Pages (from-to)583-594
Number of pages12
JournalCancer Research
Volume73
Issue number2
Early online date27 Nov 2012
DOIs
Publication statusPublished - 15 Jan 2013

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    Baker, A-M., Bird, D., Welti, J. C., Gourlaouen, M., Lang, G., Murray, G. I., Reynolds, A. R., Cox, T. R., & Erler, J. T. (2013). Lysyl oxidase plays a critical role in endothelial cell stimulation to drive tumor angiogenesis. Cancer Research, 73(2), 583-594. https://doi.org/10.1158/0008-5472.CAN-12-2447