Accession Number:

ADA409628

Title:

Cell Surface Molecules Driving Breast Cancer/Endothelial Interactions

Descriptive Note:

Annual summary rept. 1 Jul 2001-30 Jun 2002

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC MEDICAL CENTER

Personal Author(s):

Report Date:

2002-07-01

Pagination or Media Count:

20.0

Abstract:

Fibroblast growth factor-binding protein 1 FGF-BP1 is a secreted heparin-binding protein that can bind and solubilize members of the fibroblast growth factor FGF family. FGF-2 is immobilized on heparan sulfate proteoglycans HSPGs in the extracellular matrix and can be released from this storage and activated by degradation of the HSPG or by binding a soluble chaperone molecule that transports it to its cell-surface tyrosine kinase receptor. FGF-BPl was proposed to serve as such a carrier protein and has been demonstrated to act as an angiogenic switch in models of malignant progression of cancer. Two recombinant FGF-BP1 proteins were produced in prokaryotic and eukaryotic expression systems, and demonstrated to bind several members of the FGF family in a dose-dependent, reversible manner Furthermore, FGF-2 binding to FGF-BPl and to heparan sulfate was found to be mutually exclusive. FGF-BPl did not interfere with FGF-2 binding to its tyrosine kinase receptor FGFR1 in a cell-free system, and the biologic effects of FGF-2 were enhanced by the addition of exogenous FGF-BPl in models of growth and angiogenesis. Finally, HIV-l Tat protein was found to inhibit FGF-2 binding to FGF-BPl but not to its receptor, suggesting that HIV-1 Tat might function as an FGF binding protein.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE