HEPARIN-BINDING GROWTH FACTOR(S) DERIVED FROM HEAD AND NECK SQUAMOUS-CELL CARCINOMAS INDUCE ENDOTHELIAL-CELL PROLIFERATION

Background. Tumor growth is dependent on the expansion and proliferati on 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. Pr evious studies in our laboratory demonstrated that head and neck squam ous cell carcinomas (HNSCC) are angiogenic in vivo. To clarify the mec hanism of HNSCC-induced angiogenesis, the present study sought to dete rmine ii HNSCCs produced endothelial cell mitogens in vitro. Methods. Production of PGE-2, TGF-beta, FGF-2 (basic-FGF [fibroblast growth fac tor]), and vascular endothelial cell growth factor (VEGF) were quantit ated by enzyme-linked immunoabsorbant assay (ELISA) in five HNSCC line s. Cell free supernatants of 5 HNSCC lines were tested in a nonradioac tive proliferation assay using human umbilical vein endothelial cell ( HUVECs). Results. Ali lines demonstrated enhanced endothelial cell pro liferation in a dose-dependent fashion. Fractionation of these superna tants by heparin column chromatography significantly reduced endotheli al 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 c ell 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. (C) 19 97 John Wiley & Sons, Inc.