title: SIVmac₂₃₉-Nef down-regulates cell surface expression of CXCR4 in tumor cells and inhibits proliferation, migration and angiogenesis.
abstract: OBJECTIVE
  To evaluate if the lentiviral accessory protein Nef can down-regulate the C-X-C chemokine receptor type 4 (CXCR4) in tumor cells and affect tumor cell proliferation, migration and angiogenesis.
  
  
  METHODS
  HeLa-(ACC) cells, which according to genotype analysis are virtually identical to the cervical cancer-derived HeLa cell line, were transfected with Nef from SIV(mac239) and expression levels of cell surface CXCR4 were monitored by flow cytometry. Real-time proliferation and migration of cells was measured with the xCELLigence system or with the in vitro scratch assay. In vitro tube formation was deployed to assess the effect of Nef on angiogenesis.
  
  
  RESULTS
  Cell surface down-regulation of CXCR4 was observed in HeLa-(ACC) cells after Nef transfection, as well as in the monkey kidney-derived COS-7 cell line after co-transfection of CXCR4 and Nef. Proliferation, as well as migration, of Nef-transfected HeLa-(ACC) cells appeared to be significantly reduced. In vitro tube formation was markedly lowered after Nef transfection, and CXCR4 knockdown with siRNA.
  
  
  CONCLUSIONS
  SIV-Nef could serve as an interesting tool to study the biological behavior of CXCR4-expressing tumor cells and could be helpful in the discovery of new therapeutic approaches for the treatment of CXCR4-positive tumors.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Marburg Campus, Baldingerstrasse, D-35033 Marburg, Germany.
authors: Chengzhong
authors: C
authors: Cai
authors: Fiona R
authors: FR
authors: Rodepeter
authors: Annette
authors: A
authors: Rossmann
authors: Afshin
authors: A
authors: Teymoortash
authors: Jin-Seok
authors: JS
authors: Lee
authors: Karl
authors: K
authors: Quint
authors: Pietro
authors: P
authors: DI Fazio
authors: Matthias
authors: M
authors: Ocker
authors: Jochen A
authors: JA
authors: Werner
authors: Robert
authors: R
authors: Mandic
mesh_terms: D000818:Animals; D019556:COS Cells; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015693:Gene Products, nef / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C527276:CXCR4 protein, human; D015693:Gene Products, nef; D019718:Receptors, CXCR4