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.
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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.)
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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
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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
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