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 four 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 extracellular domain mutant, which has markedly diminished function for activation of factor X. Cells transfected with the full-length antisense TF sequence produced decreased levels of both TF and VEGF. Transfectants with the extracellular domain mutant produced high levels of VEGF mRNA. However, cells transfected with the cytoplasmic deletion mutant construct produced increased levels of TF, but little or no VEGF. Thus, the cytoplasmic tail of TF may signal VEGF expression in some tumor cells.
Zhang
Jing
J
State Key Lab for GI Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
Ding
Jie
J
Zhang
Xueyong
X
Shao
Xiaodong
X
Hao
Zhiming
Z
D000818:Animals; D016373:DNA, Antisense / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D016373:DNA, Antisense; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin