期刊
CANCER RESEARCH
卷 72, 期 15, 页码 3851-3863出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-11-3951
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类别
资金
- Canadian Institutes for Health Research [MOP 89714, MOP 119589, PLS 95381]
- Cancer Research Society
- Canadian Breast Cancer Foundation
- CIHR
- Natural Sciences and Engineering Research Council Alexander Graham Bell Canada Graduate Scholarship
- Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at CIHR [TGT-53912]
- MacDonald Scholarship for the Canadian Heart and Stroke Foundation
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. (C) 2012 AACR.
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