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

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.

• Authors: E R Sauter, M Nesbit, D Tichansky, Z J Liu, T Shirakawa, J Palazzo, M Herlyn
• Journal: International journal of cancer (Int J Cancer) Vol. 92 Issue 3 Pg. 374-81 (May 01 2001) ISSN: 0020-7136 [Print] United States
• PMID: 11291074 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Antibodies, Monoclonal
• Carrier Proteins
• Intercellular Signaling Peptides and Proteins
• Fibroblast Growth Factor 2
• FGFBP1 protein, human
• RNA

Topics

• Antibodies, Monoclonal
• Antibody Specificity
• Carcinogenicity Tests
• Carcinoma, Squamous Cell (immunology, metabolism, pathology)
• Carrier Proteins (biosynthesis, genetics, immunology, metabolism)
• Cell Division (genetics)
• Dimerization
• Disease Progression
• Fibroblast Growth Factor 2 (biosynthesis, genetics, metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins
• Keratinocytes (cytology, immunology, metabolism)
• Phenotype
• RNA (biosynthesis)
• Transduction, Genetic
• Tumor Cells, Cultured