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 n ormal and malignant cells. However, bFGF cannot exert its effects unless it gets outside of the cell. Since it lacks a signal sequence to direct secre tion, the method by which tells release it remains unclear. A 17 kDa secret ed 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 mR NA expression in normal keratinocytes was higher than in 5/5 SCCs, Using a new monoclonal antibody, we demonstrate that FGF-BP can dimerize, Immunoass ays demonstrate that normal keratinocytes have a higher level of FGF-BP tha n SCCs, In normal human squamous epithelium, we observed diffuse, moderate to intense cytoplasmic and membranous expression of FGF-BP, Expression decr eased and became focal with disease progression to invasive cancer. Injecti on of immortalized but non-tumorigenic HaCaT cells transduced with FGF-BP i nto normal human skin xenografts failed to result in tumors. Transfection o f FCF-BP into the SCCs Det 562 and FaDu did not promote tumor growth more t han controls, and peri-tumoral microvessel density was lower in FGF-BP-tran sfected than in control tumors. Taken together, these data suggest that FCF -BP expression in squamous epithelium doer not play an important role in pr ogression to invasive carcinoma. (C) 2001 Wiley-Liss. Inc.