title: Distinct profile of vascular progenitor attachment to extracellular matrix proteins in cancer patients.
abstract: BACKGROUND
  Vascular progenitor cells (VPCs) facilitate angiogenesis and initiate vascular repair by homing in on sites of damage and adhering to extracellular matrix (ECM) proteins. VPCs also contribute to tumor angiogenesis and induce angiogenic switching in sites of metastatic cancer. In this study, the binding of attaching cells in VPC clusters that form in vitro on specific ECM proteins was investigated.
  
  
  METHODS
  VPC cluster assays were performed in vitro on ECM proteins enriched in cancer cells and in remodelling tissue. Profiles of VPC clusters from patients with cancer were compared to healthy controls. The role of VEGF and integrin-specific binding of angiogenic attaching cells was addressed.
  
  
  RESULTS
  VPC clusters from cancer patients were markedly increased on fibronectin relative to other ECM proteins tested, in contrast to VPC clusters from control subjects, which formed preferentially on laminin. Specific integrin-mediated binding of attaching cells in VPC clusters was matrix protein-dependent. Furthermore, cancer patients had elevated plasma VEGF levels compared to healthy controls and VEGF facilitated preferential VPC cluster formation on fibronectin. Incubating cells from healthy controls with VEGF induced a switch from the 'healthy' VPC binding profile to the profile observed in cancer patients with a marked increase in VPC cluster formation on fibronectin.
  
  
  CONCLUSIONS
  The ECM proteins laminin and fibronectin support VPC cluster formation via specific integrins on attaching cells and can facilitate patterns of VPC cluster formation that are distinct in cancer patients. Larger studies, however, are needed to gain insight on how tumor angiogenesis may differ from normal repair processes.
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Labonté
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Christina L
authors.initials: CL
authors.lastname: Addison
authors.forename: Marjorie
authors.initials: M
authors.lastname: Brand
authors.forename: Hedyeh
authors.initials: H
authors.lastname: Javidnia
authors.forename: Martin
authors.initials: M
authors.lastname: Corsten
authors.forename: Kevin
authors.initials: K
authors.lastname: Burns
authors.forename: David S
authors.initials: DS
authors.lastname: Allan
mesh_terms: D000328:Adult; D000368:Aged; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D042461:Vascular Endothelial Growth Factor A