Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium.
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.
Sauter
E R
ER
The Wistar Institute, Philadelphia, PA, USA.
Nesbit
M
M
Tichansky
D
D
Liu
Z J
ZJ
Shirakawa
T
T
Palazzo
J
J
Herlyn
M
M
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D015197:Carcinogenicity Tests; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D019281:Dimerization; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D012313:RNA / Q000096:biosynthesis; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2; C070699:FGFBP1 protein, human; D012313:RNA