Soluble tissue factor has unique angiogenic activities that selectively promote migration and differentiation but not proliferation of endothelial cells.
The level of circulating tissue factor (TF) is up-regulated in human angiogenesis-related malignancies. However, whether circulating TF has angiogenic activities has not been determined. Soluble TF (sTF) is the main domain of circulating TF. Here, using cell migration, wound healing, and tubule formation assays, human recombinant sTF was found to significantly promote the migration and differentiation of endothelial cells. The stress fiber formation and rearrangement induced by sTF observed through immunofluorescence microscope may be responsible for the stimulatory migration effect of sTF. Nevertheless, sTF had no effects on endothelial cell proliferation. Interestingly, sTF can be internalized by endothelial cells, which implies a novel mechanism for sTF in angiogenesis. These results suggest that sTF has unique angiogenic activities and may serve as a potential therapeutic target to treat diseases associated with angiogenesis such as cancer and rheumatoid arthritis.
He
Yingbo
Y
Laboratory of Protein Chemistry, Beijing Key Laboratory for Protein Therapeutics, Department of Biological Sciences & Biotechnology, Tsinghua University, Qinghua Yuan 1, Beijing 100084, China.
Chang
Guodong
G
Zhan
Shunli
S
Song
Xiaomin
X
Wang
Xiaofeng
X
Luo
Yongzhang
Y
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D011994:Recombinant Proteins; D013925:Thromboplastin