Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice
Research output: Contribution to journal › Journal article › Research › peer-review
The plasminogen activator inhibitor-1 (PAI-1) blocks the activation of plasmin(ogen), an extracellular protease vital to cancer invasion. PAI-1 is like the corresponding plasminogen activator uPA (urokinase-type plasminogen activator) consistently expressed in human breast cancer. Paradoxically, high levels of PAI-1 as well as uPA are equally associated with poor prognosis in cancer patients. PAI-1 is thought to play a vital role for the controlled extracellular proteolysis during tumor neovascularization. We have studied the effect of PAI-1 deficiency in a transgenic mouse model of metastasizing breast cancer. In these tumors, the expression pattern of uPA and PAI-1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis. In a cohort of 63 transgenic mice that were either PAI-1-deficient or wild-type sibling controls, primary tumor growth and vascular density were unaffected by PAI-1 status. PAI-1 deficiency also did not significantly affect the lung metastatic burden. These results agree with the virtual lack of spontaneous phenotype in PAI-1-deficient mice and humans and may reflect that the plasminogen activation reaction is not rate limiting for tumor vascularization and metastasis, or that there is a functional redundancy between PAI-1 and other inhibitors of the uPA/plasmin system, masking the effect of PAI-1 deficiency.
Original language | English |
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Journal | Oncogene |
Volume | 22 |
Issue number | 28 |
Pages (from-to) | 4389-4397 |
ISSN | 0950-9232 |
DOIs | |
Publication status | Published - 2003 |
Bibliographical note
Keywords: plasminogen activator inhibitor-1 (PAI-1), metastasis, breast cancer, angiogenesis
ID: 113307