title: Endothelial cell-secreted EGF induces epithelial to mesenchymal transition and endows head and neck cancer cells with stem-like phenotype.
abstract: Emerging evidence suggests that endothelial cell-secreted factors contribute to the pathobiology of squamous cell carcinoma (SCC) by enhancing invasive migration and resistance to anoikis. Here, we report that SCC cells within the perivascular niche have undergone epithelial to mesenchymal transition (EMT) in a primary human SCC of a patient that developed distant metastases. Endothelial cell-secreted EGF induced EMT of human SCC cells in vitro and also induced acquisition of a stem-like phenotype. In vivo, tumor xenografts vascularized with EGF-silenced endothelial cells exhibited a smaller fraction of cancer stem-like cells (ALDH(+)CD44(+)) and were less invasive than tumors vascularized with control endothelial cells. Collectively, these results demonstrated that endothelial cell-EGF induces EMT and acquisition of stem-like properties by head and neck tumor cells. On this basis, we suggest that vascular endothelial cells contribute to tumor dissemination by secreting factors that endow carcinoma cells with enhanced motility and stemness.
authors.affiliation: Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Zhaocheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Isabel S
authors.initials: IS
authors.lastname: Lauxen
authors.affiliation: Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Manoel Sant'Ana
authors.initials: MS
authors.lastname: Filho
authors.affiliation: Authors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, BrazilAuthors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, BrazilAuthors' Affiliations: Department of Restorative Sciences, Angiogenesis Research Laboratory, University of Michigan School of Dentistry; Department of Biomedical Engineering, University of Michigan College of Engineering; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan; and Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil jenor@umich.edu.
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nör
mesh_terms: D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt