Regulation of fibroblast growth factor-2 activity by human ovarian cancer tumor endothelium.
AuthorsWhitworth, Melissa K
Backen, Alison C
Clamp, Andrew R
Wilson, Godfrey E
McVey, Rhona J
Rapraeger, Alan C
McGown, Alan T
Slade, Richard J
Gallagher, John T
Jayson, Gordon C
AffiliationCancer Research UK Department of Medical Oncology, Christie Hospital and Paterson Institute, Manchester, United Kingdom.
MetadataShow full item record
AbstractFibroblast growth factor-2 (FGF-2) is a potent angiogenic cytokine that is dependent on heparan sulfate for its biological activity. We have investigated the relationship among heparan sulfate, FGF-2, and the signal-transducing receptors in human, advanced-stage, serous ovarian adenocarcinoma. Using a unique molecular probe, FR1c-Ap, which consisted of a soluble FGF receptor 1 isoform IIIc covalently linked to an alkaline phosphatase moiety, the distribution of heparan sulfate that had the ability to support the formation of a heparan sulfate/FGF-2/FGFR1 isoform IIIc alkaline phosphatase heparan sulfate construct complex was determined. This may be taken as a surrogate marker for the distribution of biologically active heparan sulfate and was distributed predominantly in endothelial cells and stroma but was absent from adenocarcinoma cells. In situ hybridization revealed the expression of FGFR1 mRNA in the endothelium and reverse transcription-PCR confirmed the presence of FGFR1 isoform IIIc but not isoform IIIb. The presence of FGF-2 around tumor endothelium was detected through immunohistochemistry. Double-staining techniques showed that heparan sulfate was found predominantly at the basal aspect of the endothelium and suggested that syndecan-3 might function as one of the proteoglycans involved in FGF-2 signaling in the endothelium. The data suggest that the entire extracellular signaling apparatus, consisting of FGF-2, biologically active heparan sulfate, and FGFRs capable of responding to FGF-2, is present in ovarian cancer endothelium, thereby highlighting the cytokine and its cognate receptor as potential targets for the antiangiogenic treatment of this disease.
CitationRegulation of fibroblast growth factor-2 activity by human ovarian cancer tumor endothelium. 2005, 11 (12):4282-8 Clin. Cancer Res.
JournalClinical Cancer Research
- In vitro changes in plasma membrane heparan sulfate proteoglycans and in perlecan expression participate in the regulation of fibroblast growth factor 2 mitogenic activity.
- Authors: Guillonneau X, Tassin J, Berrou E, Bryckaert M, Courtois Y, Mascarelli F
- Issue date: 1996 Jan
- Heparan sulfate proteoglycans function as receptors for fibroblast growth factor-2 activation of extracellular signal-regulated kinases 1 and 2.
- Authors: Chua CC, Rahimi N, Forsten-Williams K, Nugent MA
- Issue date: 2004 Feb 20
- Basic fibroblast growth factor (bFGF) dissociates rapidly from heparan sulfates but slowly from receptors. Implications for mechanisms of bFGF release from pericellular matrix.
- Authors: Moscatelli D
- Issue date: 1992 Dec 25
- A soluble fibroblast growth factor receptor is released from HL-60 promyelocytic leukemia cells: implications for paracrine growth control.
- Authors: Wang JF, Shen M, Fong GH, Hill DJ
- Issue date: 2000
- HSulf-1 inhibits angiogenesis and tumorigenesis in vivo.
- Authors: Narita K, Staub J, Chien J, Meyer K, Bauer M, Friedl A, Ramakrishnan S, Shridhar V
- Issue date: 2006 Jun 15