Expression of basic fibroblast growth factor protein and its down-regulation by interferons in head and neck cancer.
BACKGROUND
Angiogenesis is crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to correlate with metastasis and aggressiveness. Basic fibroblast growth factor (bFGF) has potent angiogenic activity and has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). Material and Methods Frozen sections of 50 HNSCC were immunostained for von Willebrand factor and bFGF. Microvessels were counted by light microscopy; bFGF expression was studied at the light and electron microscopic level. Laryngeal cancer cell line HlaC79 was incubated with interferon (IFN) alpha and beta. bFGF quantification was performed by ELISA, and antiproliferative effects were determined by BrdU assay.


RESULTS
The mean number of blood vessels (77.5 +/- 23.7) is significantly increased in HNSCC compared with controls (17.1 +/- 5.9). bFGF protein expression was detected in all HNSCC but not in control tissue. An correlation between bFGF expression and mean number of microvessels was found (p <.001). However, no correlation between bFGF expression and the main clinicopathologic features was shown. The long-term exposure (144 hr) of HNSCC cells to noncytostatic concentrations of IFN alpha and beta (>10 U/mL) down-regulated the protein production of bFGF.


CONCLUSIONS
bFGF expression and angiogenesis are enhanced in HNSCC. The higher microvessel density in HNSCC with strong bFGF expression supports the importance of bFGF for tumor angiogenesis. IFN alpha and beta treatment leads to a down-regulation of bFGF expression independent of their antiproliferative effects, suggesting that IFN treatment might result in a reduction of angiogenesis in HNSCC.
Riedel
F
F
Department of Otolaryngology, Head and Neck Surgery, University Hospital Mannheim, D-68135 Mannheim, Germany.
Götte
K
K
Bergler
W
W
Rojas
W
W
Hörmann
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D046508:Culture Techniques; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D011379:Prognosis; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D016898:Interferon-alpha; D016222:Fibroblast Growth Factor 2