Tumor vascularization is requisite for breast cancer progression, and high microvascular density in tumors is a poor prognostic indicator. Patients bearing breast cancers expressing human embryonic stem cell (hESC)-associated genes similarly exhibit high mortality rates, and the expression of embryonic proteins is associated with tumor progression. Here, we show that Nodal, a hESC-associated protein, promotes breast cancer vascularization. We show that high levels of Nodal are positively correlated with high vascular densities in human breast lesions (P = 0.0078). In vitro, we show that Nodal facilitates breast cancer-induced endothelial cell migration and tube formation, largely by upregulating the expression and secretion of proangiogenic factors by breast cancer cells. Using a directed in vivo angiogenesis assay and a chick chorioallantoic membrane assay, we show that Nodal promotes vascular recruitment in vivo. In a clinically relevant in vivo model, whereby Nodal expression was inhibited following tumor formation, we found a significant reduction in tumor vascularization concomitant with elevated hypoxia and tumor necrosis. These findings establish Nodal as a potential target for the treatment of breast cancer angiogenesis and progression. ©2012 AACR.
CITATION STYLE
Quail, D. F., Walsh, L. A., Zhang, G., Findlay, S. D., Moreno, J., Fung, L., … Postovit, L. M. (2012). Embryonic protein nodal promotes breast cancer vascularization. Cancer Research, 72(15), 3851–3863. https://doi.org/10.1158/0008-5472.CAN-11-3951
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