Supplementary Methods from Embryonic Protein Nodal Promotes Breast Cancer Vascularization

Quail, Daniela F.; Walsh, Logan A.; Zhang, Guihua; Findlay, Scott D.; Moreno, Juan; Fung, Laura; Ablack, Amber; Lewis, John D.; Done, Susan J.; Hess, David A.; Postovit, Lynne-Marie

doi:10.1158/0008-5472.22392929.v1

00085472can113951-sup-meth_153k.pdf (153.53 kB)

Supplementary Methods from Embryonic Protein Nodal Promotes Breast Cancer Vascularization

journal contribution

posted on 2023-03-30, 21:10 authored by Daniela F. Quail, Logan A. Walsh, Guihua Zhang, Scott D. Findlay, Juan Moreno, Laura Fung, Amber Ablack, John D. Lewis, Susan J. Done, David A. Hess, Lynne-Marie Postovit

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ARTICLE ABSTRACT

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. Cancer Res; 72(15); 3851–63. ©2012 AACR.