Embryonic Protein Nodal Promotes Breast Cancer Vascularization

作者：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^*

来源：Cancer Research, 2012, 72(15): 3851-3863.

DOI：10.1158/0008-5472.CAN-11-3951

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.

• 出版日期2012-8-1