title: Embryonic protein nodal promotes breast cancer vascularization.
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.
authors.affiliation: Department of Anatomy & Cell Biology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Quail
authors.forename: Logan A
authors.initials: LA
authors.lastname: Walsh
authors.forename: Guihua
authors.initials: G
authors.lastname: Zhang
authors.forename: Scott D
authors.initials: SD
authors.lastname: Findlay
authors.forename: Juan
authors.initials: J
authors.lastname: Moreno
authors.forename: Laura
authors.initials: L
authors.lastname: Fung
authors.forename: Amber
authors.initials: A
authors.lastname: Ablack
authors.forename: John D
authors.initials: JD
authors.lastname: Lewis
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Done
authors.forename: David A
authors.initials: DA
authors.lastname: Hess
authors.forename: Lynne-Marie
authors.initials: LM
authors.lastname: Postovit
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D002642:Chick Embryo; D018450:Disease Progression; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055153:Stem Cell Niche / Q000235:genetics; D014162:Transfection
chemical_list: C526007:NODAL protein, human; D055457:Nodal Protein