Head and neck squamous cell carcinoma lines produce biologically active angiogenic factors

Angiogenesis is the formation of capillaries from pre-existing blood vessels. Angiogenesis occurs in many developmental, physiologic, and pathologic processes including tumor growth. Previous studies have shown that angiogenesis is required for growth and metastasis of solid tumors. Fibroblast growth factors (FGF-1, -2) and vascular endothelial growth factor (VEGF) are extremely potent angiogenesis inducers by stimulating the proliferation and migration of capillary endothelial cells. Expression of these factors is upregulated in many solid tumors and correlates with high vascularity, lymph node metastasis, and poor clinical prognosis. Few studies have examined whether established head and neck squamous cell carcinoma (SCC) lines produce biologically active angiogenic factors. By immunoprecipitation, we detected FGF and VEGF proteins in cellular lysates of SCC lines. We also detected FGF-1 and -2 proteins in serum-free-conditioned medium from these lines. Conditioned medium from SCC lines significantly increased proliferation of human umbilical vein endothelial cells (HUVEC). This increased proliferation was abrogated by pre-incubation of conditioned medium with neutralizing antibodies to FGFs and VEGF. Conditioned medium from SCC lines also significantly stimulated HUVEC invasion across a reconstituted basement membrane. We concluded that head and neck SCC lines secrete biologically active angiogenic factors.