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.
The PIP2 pathway seems to provide a link between oncogene-associated transformation, cellular proliferation, plasminogen-activator expression and tumour invasion and metastasis.
Plasmin, the major fibrinolytic enzyme in blood, also participates in a number of physiologic functions involving protein processing and tissue remodelling, and may play an important role in tumor invasion and metastasis.
These findings indicate that cancer cells themselves produce u-PA, and suggest that u-PA converts plg into plasmin, which dissolves the extracellular matrix surrounding cancer cells, resulting in cancer invasion and metastasis.
Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis.
The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis.
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.
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.
Tumour-associated proteinases, matrix metalloproteinases and plasminogen activators are reported to be involved in pancreatic cancer 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.
The recent immunohistochemical finding that invasive esophageal carcinomas express elevated levels of urokinase (uPA) and urokinase receptor (uPA-R) in vivo suggest that the plasminogen activation system may contribute to metastasis in esophageal cancer.
Because no data are available on the involvement of the plasmin activation system in matrix degradation by thyroid carcinoma, the present study was performed using follicular thyroid carcinoma cell lines obtained from a primary tumor (FTC-133) and metastases (FTC-236 and FTC-238) of one patient.
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.
It was recently discovered, however, that bikunin effectively inhibits a proteinase that seems to be involved in the metastasis of tumour cells--cell surface plasmin--and that a fragment of bikunin inhibits two proteinases of the coagulation pathway--factor Xa and kallikrein.
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.
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.
These findings suggest that VEGF-B may contribute to tumour progression by a non-angiogenic mechanism, possibly by increasing plasminogen activators and hence metastasis, as has been described in vitro.
These data suggest that the invasive and metastatic potential of human large-cell lung carcinoma cell lines is associated with differential expressions of the components of the plasminogen activator system and that the determination of these components may be used as a marker for judging clinically the possibility of tumor metastasis as well as the prognoses of patients.
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.