The Influence Of Tissue Factor To The Invasion And Hematogenous Metastasis Of Tumor Cells

Tissue factor, also called coagulation factorⅢ, is a kind of trans-membrane glucoprotein which has 263 amino-acid residues. Tissue factor was known as the initiation factor of extrinsic coagulation pathway. For the past few years, the variety of the tissue factor function have been found. The relations of tissue factor and tumor invasion and metastasis have become the hotspot.Tissue factor was normally expressed in the macrophage, fibroblast cell, adventitia and part endothelial cells. In tumor tissue, tissue factor was expressed in the tumor cell and vessel endothelial cells. The high expression of tissue factor in tumor cell directly influence the biodiversity of tumor cell, especially the tumor cell proliferation, invasion and hematogenous metastasis. It was confirmed by flow cytometry and immunofluorescence staining that tissue factor(TF) had high expression in fibrosarcoma cell(HT1080).But the mechanism of the influence of tissue factor to tumor invasion and hematogenous metastasis was still unclear.The process of hematogenous metastasis is a multi-steps and complex biologic event.1) primary tumor cell proliferation and separation from the tumor.2) tumor cell intravascular migration.3) the subsequent extravascular migration.4) metastasis to the target organ and proliferation. Especially the the intravascular migration and the subsequent extravascular migration of tumor cells are the critical steps in hematogenous metastasis. The migration of tumor cells is achieved by the interaction of tumor cell and vascular endothelial cell. To study hematogenous metastasis of tumor cells, the vascular wall was simulated by the construction of monolayer vascular endothelial cells and extra-cellular matrix. The models of intravascular migration and extravascular migration were constructed by adding tumor cells in different direction. The human umbilical venous endothelial cell(HUVEC) was used to construct the monolayer vascular endothelial cell wall and collagen was used to simulate the extra-cellular matrix. The crucial step of the research is the construction of the. The Giemsa stain was used to observe the development of the monolayer vascular endothelial cell wall and the suitable resistance value was 9.09±1.6ohm/cm2 which agreed with other research. HT1080 migrated and passed through the collagen gel and the monolayer vascular endothelial cell to the surface. This process was like intravascular migration of tumor cells in vivo. HT1080 also migrated and passed through the monolayer vascular endothelial cells to the collagen gel. This process was like extravascular migration of tumor cells in vivo. The antibody of tissue factor inhibited intravascular and extravascular migration of tumor cells and the inhibition was concentration-dependent. The receptor of tissue factor was expressed on the surface of the vascular endothelial cell. Combing the the pre-study of the endothelial signal transduction mechanism, it was thought that tissue factor which expressed on the tumor cell combined to the ligand on the vascular endothelial cell through the extracellular 202-219 amino-acid. The combination conducted the variation of the vascular endothelial cell and caused hematogenous metastasis of tumor cells.The invasion of the tumor cell is also a kind of complex biologic event. We constructed the matrix invasion model of the tumor cell and mimicked the matrix invasion process of tumor cell in vivo. We found that HT1080 could get through the collagen gel and antibody of tissue factor could inhibit this process. The inhibition was concentration-dependent. It had been proved that tissue factor participate in the tumor invasion and hematogenous metastasis. Although the mechanism was not very clearly and the research is still in process, tissue factor have become one of the most attractive antitumor target protein. The prospect of tissue factor targeting antitumor treatment is vast and extensive.