Heparin-binding growth factor(s) derived from head and neck squamous cell carcinomas induce endothelial cell proliferations.
BACKGROUND
Tumor growth is dependent on the expansion and proliferation of the host vascular system into the primary neoplasm (angiogenesis). The development of an intact vascular system requires migration and proliferation of endothelial cells and assembly into microvessels. Previous studies in our laboratory demonstrated that head and neck squamous cell carcinomas (HNSCC) are angiogenic in vivo. To clarify the mechanism of HNSCC-induced angiogenesis, the present study sought to determine if HNSCCs produced endothelial cell mitogens in vitro.


METHODS
Production of PGE-2, TGF-beta, FGF-2 (basic-FGF [fibroblast growth factor]), and vascular endothelial cell growth factor (VEGF) were quantitated by enzyme-linked immunoabsorbant assay (ELISA) in five HNSCC lines. Cell free supernatants of 5 HNSCC lines were tested in a nonradioactive proliferation assay using human umbilical vein endothelial cells (HUVECs).


RESULTS
All lines demonstrated enhanced endothelial cell proliferation in a dose-dependent fashion. Fractionation of these supernatants by heparin column chromatography significantly reduced endothelial cell proliferation in the five lines tested (range, 31.7% to 46.23% reduction; mean, 38.14+/-6.02%). Pretreatment with antibody to VEGF but not transforming growth factor (TGF)-beta inhibited endothelial cell proliferation.


CONCLUSIONS
These studies indicate HNSCCs produce factor(s) which stimulate endothelial cell proliferation and that VEGF may be involved in HNSCC-induced endothelial cell mitogenesis.
Petruzzelli
G J
GJ
Department of Otolaryngology-Head and Neck Surgery, Loyola University Medical Center, Cancer Center, Maywood, Illinois 60153, USA.
Benefield
J
J
Taitz
A D
AD
Fowler
S
S
Kalkanis
J
J
Scobercea
S
S
West
D
D
Young
M R
MR
D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000503:physiopathology; D002455:Cell Division; D002846:Chromatography, Affinity; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000503:physiopathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016228:Endothelial Growth Factors; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D015232:Dinoprostone