Regulation of vascular endothelial growth factor (VEGF) production and angiogenesis by tissue Factor (TF) in SGC-7901 gastric cancer cells.

Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is expressed in a wide range of cancer cells and plays important roles in cancer progression and metastasis. We demonstrated between TF and vascular endothelial growth factor (VEGF) production differences in 4 human gastric cell lines. One of these cell lines, SGC-7901, a high TF and VEGF producer, was grown subcutaneously in severe combined immuno-deficient (SCID) mice. The SCID mice generated solid tumors characterized by intense vascularity. In contrast, SGC-7901 cells transfected with antisense TF cDNA generated relatively avascular tumors in SCID mice, as determined by immunohistochemical staining of tumor vascular endothelial cells with anti-VIII factor antibody. To investigate the structure-function relationship between TF and VEGF, the SGC-7901 cell line was transfected with antisense a full-length TF cDNA, a cytoplasmic deletion mutant lacking the distal three serine residues (potential substrates for protein kinase C), or an ...