title: Expression of a Secreted Fibroblast Growth Factor Binding Protein-1 (FGFBP1) in Angioproliferative Kaposi Sarcoma.
abstract: OBJECTIVE
  Kaposi's sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGF-binding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the pathogenesis of AIDS-KS.
  
  
  METHODS
  BP1 was localized in AIDS-KS lesions by immunohistochemistry and in situ hybridization studies. The binding of radiolabeled FGF-2 to His-tagged BP1 or the FGF-receptor 1 was assessed in the presence and absence of HIV-Tat and other viral proteins. Mice carrying tetracycline-regulated BP1 transgene mice were used to determine whether activation of BP1 during wound healing induces KS-like lesions.
  
  
  RESULTS
  BP1 expression was detected in AIDS-KS tumor keratinocytes, spindle cells, and infiltrating mononuclear cells. In addition, HIV-Tat competed for the binding of FGF-2 to immobilized BP1, but does not affect the interactions of FGF-2 with its high affinity receptor (FGFR-1). In contrast, two other HIV-proteins, Nef and gp120, did not affect the binding of FGF-2 to BP1 or to FGFR-1. Finally, up-regulation of BP1 expression in tetracycline-regulated -conditional BP1 transgenic mice subjected to skin wounds, induced KS-like skin lesions.
  
  
  CONCLUSIONS
  Taking into consideration the results of previous studies showing that both HIV-Tat and BP1 enhance the mitogenic and angiogenic activity of locally-stored FGF-2, bothin vitroandin vivo, our findings suggest a novel mechanism by which the release and activity of FGFs can be modulated in AIDS-KS tumors by HIV-Tat as well as BP1.
authors.affiliation: Children's Research Institute, Children's National Medical Center, The George Washington University, Washington DC, USA.
authors.forename: Patricio E
authors.initials: PE
authors.lastname: Ray
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington DC, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Attar
authors.affiliation: Children's Research Institute, Children's National Medical Center, The George Washington University, Washington DC, USA.
authors.forename: Xue-Hui
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Children's Research Institute, Children's National Medical Center, The George Washington University, Washington DC, USA.
authors.forename: Jharna R
authors.initials: JR
authors.lastname: Das
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington DC, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Tassi
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington DC, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Wellstein
keywords: Angiogenesis; Endothelial cells; FGF- 2 binding; FGF-2 release; Fibroblast growth factor; HIV-Tat; KS spindle cells; Kaposi’s sarcoma; Pediatric AIDS