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Heparin‐binding growth factor(s) derived from head and neck squamous cell carcinomas induce endothelial cell proliferation
Author(s) -
Petruzzelli Guy J.,
Benefield Janet,
Taitz Ari D.,
Fowler Sarah,
Kalkanis James,
Scobercea Sebastian,
West Derrick,
Young M. Rita I.
Publication year - 1997
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/(sici)1097-0347(199710)19:7<576::aid-hed3>3.0.co;2-4
Subject(s) - endothelial stem cell , angiogenesis , cell growth , vascular endothelial growth factor , cell culture , biology , human umbilical vein endothelial cell , vascular endothelial growth factor a , basic fibroblast growth factor , cancer research , growth factor , cell , fibroblast growth factor , head and neck squamous cell carcinoma , microbiology and biotechnology , chemistry , in vitro , cancer , biochemistry , receptor , vegf receptors , genetics , head and neck cancer
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. © John Wiley & Sons, Inc. Head Neck 19 : 576–582, 1997.