Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated kunitz-type serine proteinase inhibitor that plays an important role in plasmin and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor angiogenesis, invasion and metastasis.
Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer.
Human tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz inhibitor that inhibits the plasmin- and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor progression, invasion, and metastasis.
This is the first report that TF may be one of the key receptors that can up-regulate expression of the plasminogen activator receptor in human cancer cells to enhance tumor invasion and metastasis.
Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases.
Urokinase plasminogen activator receptor (uPAR) binds pro-urokinase plasminogen activator (pro-uPA) and thereby localizes it near plasminogen, causing the generation of active uPA and plasmin on the cell surface. uPAR and uPA are overexpressed in a variety of human tumors and tumor cell lines, and expression of uPAR and uPA is highly correlated to tumor invasion and metastasis.
Recent work indicates that activation of the MET oncogene, which drives invasion and metastasis in cancer, can promote a cancer-associated thrombohemorrhagic syndrome that is mediated by transcriptional up-regulation of the procoagulation factors plasminogen activator inhibitor type-1 and cyclooxygenase-2.
The expression of the metastasis associated genes urokinase plasminogen activator, insulinlike growth factor binding protein-1 and insulinlike growth factor binding protein-3 are regulated in response to heterotypic contact and soluble factors respectively.
To know the effects of sex steroids on the potentials of growth, invasion, and metastasis with neovascularization of endometrial cancer, the expression of plasminogen activator inhibitor (PAI)-1 [an inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA)] and its mRNA in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by an enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction-Southern blotting (RT-PCR-SB), respectively, under the influence of sex steroids.
Moreover, flavokawain B significantly inhibits matrix metalloproteinase-9 and urokinase plasminogen activator expression, whereas tissue inhibitor of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 were increased, which are playing critical role in tumor metastasis.
The PIP2 pathway seems to provide a link between oncogene-associated transformation, cellular proliferation, plasminogen-activator expression and tumour invasion and metastasis.
The components of the plasminogen activation system (PAS) and the metalloproteinase family [mainly matrix metalloproteinases (MMPs)] are overexpressed in malignant tumors, driving the local invasion, metastasis and angiogenesis.
Tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz inhibitor that inhibits plasmin and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor progression, invasion and metastasis.
The high expression of metastasis-related genes, including the urokinase plasminogen activator system, metalloproteinases and vascular endothelial growth factor-C, might be attributed to the high metastatic potential in both models.
Since tetranectin binds to plasminogen we hypothesize that it could function as an anchor and/or reservoir for plasminogen and similar substances that regulate tumor invasion and metastasis as well as tumor angiogenesis.
It is a specific cell surface receptor for its ligand uPA which catalyzes the formation of plasmin from plasminogen to generate the proteolytic cascade that contributes to the breakdown of extracellular matrix, a key step in cancer metastasis.
Angiostatin protein, which comprises the first four kringle domains of plasminogen, is an endogenous inhibitor of angiogenesis that inhibits the growth of experimental primary and metastatic tumors.
The binding of uPA with uPAR is instrumental for the activation of plasminogen to plasmin, which in turn initiates a series of proteolytic cascade to degrade the components of the extracellular matrix, and thereby, cause tumor cell migration from the primary site of origin to a distant secondary organ.
There is substantial evidence that high concentrations of the urokinase plasminogen-activating system are conducive to tumour cell spread and metastasis.
It is well known that a urokinase-type plasminogen activator receptor (uPAR) is a key protein in the plasminogen activation system, which plays a proteolytically important role in the invasion and metastasis of various cancer cells.