title: VEGF-mediated angiogenesis links EMT-induced cancer stemness to tumor initiation.
abstract: An epithelial-mesenchymal transition (EMT) underlies malignant tumor progression and metastatic spread by enabling cancer cells to depart from the primary tumor, invade surrounding tissue, and disseminate to distant organs. EMT also enriches for cancer stem cells (CSC) and increases the capacity of cancer cells to initiate and propagate tumors upon transplantation into immune-deficient mice, a major hallmark of CSCs. However, the molecular mechanisms promoting the tumorigenicity of cancer cells undergoing an EMT and of CSCs have remained widely elusive. We here report that EMT confers efficient tumorigenicity to murine breast cancer cells by the upregulated expression of the proangiogenic factor VEGF-A and by increased tumor angiogenesis. On the basis of these data, we propose a novel interpretation of the features of CSCs with EMT-induced, VEGF-A-mediated angiogenesis as the connecting mechanism between cancer cell stemness and tumor initiation.
authors.affiliation: Authors' Affiliations: Department of Biomedicine, University of Basel; and Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Fantozzi
authors.forename: Dorothea C
authors.initials: DC
authors.lastname: Gruber
authors.forename: Laura
authors.initials: L
authors.lastname: Pisarsky
authors.forename: Chantal
authors.initials: C
authors.lastname: Heck
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yilmaz
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meyer-Schaller
authors.forename: Karen
authors.initials: K
authors.lastname: Cornille
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hopfer
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bentires-Alj
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse