Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium

Edward R. Sauter, Mark Nesbit, David Tichansky, Zhao-Jun Liu, Takashi Shirakawa, Juan Palazzo, Meenhard Herlyn

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Basic fibroblast growth factor (bFGF) is synthesized by a wide variety of normal and malignant cells. However, bFGF cannot exert its effects unless it gets outside of the cell. Since it lacks a signal sequence to direct secretion, the method by which cells release it remains unclear. A 17 kDa secreted binding protein for bFGF (FGF-BP, HBp-17) is expressed at high levels in squamous cell carcinoma (SCC) and transformed keratinocytes and may act as a chaperone to transport bFGF outside of the cell. In our study, FGF-BP mRNA expression in normal keratinocytes was higher than in 5/5 SCCs. Using a new monoclonal antibody, we demonstrate that FGF-BP can dimerize. Immunoassays demonstrate that normal keratinocytes have a higher level of FGF-BP than SCCs. In normal human squamous epithelium, we observed diffuse, moderate to intense cytoplasmic and membranous expression of FGF-BP. Expression decreased and became focal with disease progression to invasive cancer. Injection of immortalized but non-tumorigenic HaCaT cells transduced with FGF-BP into normal human skin xenografts failed to result in tumors. Transfection of FGF-BP into the SCCs Det 562 and FaDu did not promote tumor growth more than controls, and peri-tumoral microvessel density was lower in FGF-BP-transfected than in control tumors. Taken together, these data suggest that FGF-BP expression in squamous epithelium does not play an important role in progression to invasive carcinoma.

Original languageEnglish
Pages (from-to)374-381
Number of pages8
JournalInternational Journal of Cancer
Volume92
Issue number3
DOIs
StatePublished - May 1 2001
Externally publishedYes

Fingerprint

Fibroblast Growth Factors
Disease Progression
Fibroblast Growth Factor 2
Carrier Proteins
Epithelium
Keratinocytes
Neoplasms
Protein Sorting Signals
Microvessels
Immunoassay
Heterografts
Transfection
Squamous Cell Carcinoma
Monoclonal Antibodies
Carcinoma
Messenger RNA
Skin
Injections
Growth

Keywords

  • Fibroblast growth factor
  • Fibroblast growth factor-binding protein
  • Squamous cell carcinoma
  • Squamous epithelium

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium. / Sauter, Edward R.; Nesbit, Mark; Tichansky, David; Liu, Zhao-Jun; Shirakawa, Takashi; Palazzo, Juan; Herlyn, Meenhard.

In: International Journal of Cancer, Vol. 92, No. 3, 01.05.2001, p. 374-381.

Research output: Contribution to journalArticle

Sauter, Edward R. ; Nesbit, Mark ; Tichansky, David ; Liu, Zhao-Jun ; Shirakawa, Takashi ; Palazzo, Juan ; Herlyn, Meenhard. / Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium. In: International Journal of Cancer. 2001 ; Vol. 92, No. 3. pp. 374-381.
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