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 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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