title: CD44+/CD24- breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties.
abstract: BACKGROUND
  Recent studies suggest that the relationship between cancer stem cells (CSCs) and the vascular niche may be bidirectional; the niche can support the growth and renewal of CSCs, and CSCs may contribute to the maintenance of the niche. There is little knowledge concerning the role of breast cancer stem cells in promoting tumor angiogenesis.
  
  
  OBJECTIVE
  For human breast cancers, CSCs have been shown to be associated with a CD44+/CD24- phenotype. We investigated the potential activities of CD44+/CD24- breast cancer stem cells in promoting tumor angiogenesis.
  
  
  METHODS
  The expression of pro-angiogenic genes was determined by quantitative real-time RT-PCR. Endothelial cell migration assays were employed to evaluate effects of conditioned media from CD44+/CD24- on human umbilical vein endothelial cells. A chorioallantoic membrane (CAM) assay was used to study the potential of CD44+/CD24- cells to promote angiogenesis.
  
  
  RESULTS
  In our study, CD44+/CD24- cells expressed elevated levels of pro-angiogenic factors compared with CD44+/CD24+ cells. CD44+/CD24- cell-conditioned media significantly increased endothelial cell migration. Breast cancer cell lines enriched with CD44+/CD24- cells were more pro-angiogenic in the CAM assay than those lacking a CD44+/CD24- subpopulation. CD44+/CD24- cells sorted from MCF-7 cell lines were more pro-angiogenic in a CAM assay than CD44+/CD24+ cells. Furthermore, the VEGF concentration was significantly higher in CD44+/CD24- cell-conditioned media than in CD44+/CD24+ cell-conditioned media. The pro-angiogenic effect of CD44+/CD24- cells on endothelial cells was abolished by bevacizumab.
  
  
  CONCLUSIONS
  Our findings demonstrate that CD44+/CD24- breast cancer stem cells have substantial pro-angiogenic potential and activity. This provides new insights to explore in the development of targeted therapies.
authors.affiliation: Duke-PKU Cancer Program, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Oncology and Immunotherapy, Beijing Cancer Hospital and Institute, Peking University School of Oncology, University Cancer Hospital, 52 Fucheng Rd, Beijing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Lijun
authors.initials: L
authors.lastname: Di
authors.forename: Guohong
authors.initials: G
authors.lastname: Song
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051927:CD24 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D000068258:Bevacizumab