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What are the clinical implications of the urokinase plasminogen activator system?

  The project name

  Urokinase plasminogen activator system.

  Reference range

  0.41 ± 0.15 ng/ml(ELISA).

  Clinical significance

What are the clinical implications of the urokinase plasminogen activator system?

  1. Urokinase plasminogen activator system has three components: urokinase plasminogen activator (uPA, a 53 kD serine protease), uPA membrane binding receptor (uPAR), and uPA inhibitors pai-1 and pai-2.

  2. UPA is a single chain inactive polypeptide, which is activated by breaking between lysine at 158 and isoleucine at 159. The activation process can be catalyzed by various proteases, including cathepsin B, L and hK2. The activated forms of uPA include A chain and B chain, A chain ACTS on uPA membrane binding receptor (uPAR), and B chain has catalytic activity. The most characteristic activity of uPA is plasminogen activation into plasminogen, which breaks down the extracellular matrix (ECM) and activates interstitial metalloproteinases (MMPs), which also breaks down ECM and activates and releases growth factors (fibroblast growth factor FGF2 and transforming growth factor TGF- beta). In vivo, uPA activity is regulated by pai-1 and pai-2 inhibitory molecules, which have other functions such as promoting angiogenesis, promoting cell adhesion and migration, and inhibiting apoptosis.

  3. UPA is used to predict the prognosis of breast cancer and other tumors.

  1) breast cancer uPA is the first protease to increase when breast cancer metastases, which is of certain value in determining prognosis. Multiple studies have confirmed that primary breast cancer patients with high uPA activity have poor prognosis, and uPA can be used as an independent prognostic indicator. UPA is comparable to lymph nodes in determining overall survival. In addition, the value of uPA is reflected in the diagnosis of breast cancer patients with negative regional lymph node tissue examination, thus avoiding unnecessary clinical chemotherapy. Pai-1 is associated with angiogenesis, inhibition of apoptosis and anti-upa, etc. Therefore, high levels of pai-1 are associated with invasive breast cancer and other tumors. The combined detection of uPA and PAI-1 can be used to predict the prognosis of breast cancer. Generally speaking, increased levels of uPA and/or PAI-1 indicate poor prognosis. Patients with uPA content less than 0.3 ng and pai-1 content less than 14 ng per mg of tissue had better prognosis.

  2) uPA of other tumors also has certain application value in determining the prognosis of colorectal cancer. It was found that uPA can determine the prognosis of patients with locally infiltrated but unmetastasized lymph nodes (Dukes stage B). Other studies have shown that uPA is helpful in determining the prognosis of a variety of tumors, including ovarian, kidney, hepatocellular, pancreatic, glioma, urinary tract, bladder, lung adenocarcinoma, and cervical cancer. Thus, uPA can be used as a "broad spectrum" prognostic marker.

  Factors affecting the

  At present, the detection method is not uniform, the batch number of monoclonal antibody is also different, the results of different detection methods are different, so that the reference value of the standard is not the same.

  methodology

  Enzyme-linked immunoassay (ELISA), immunohistochemistry.