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Fibroblast growth factor–binding protein expression changes with disease progression in clinical and experimental human squamous epithelium
Author(s) -
Sauter Edward R.,
Nesbit Mark,
Tichansky David,
Liu ZhaoJun,
Shirakawa Takashi,
Palazzo Juan,
Herlyn Meenhard
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1207
Subject(s) - transfection , fibroblast growth factor , biology , basic fibroblast growth factor , epithelium , cancer research , hacat , fibroblast , cell culture , pathology , tumor progression , growth factor , cancer , medicine , receptor , biochemistry , genetics
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. © 2001 Wiley‐Liss, Inc.