Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation
- 1 August 1996
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 317 (3) , 763-769
- https://doi.org/10.1042/bj3170763
Abstract
Cell-surface activation of plasminogen may be important in diseases that involve cellular migration, including atherosclerosis and tumour invasion/metastasis. Cytokeratin 8 (CK 8) has been identified as a plasminogen-binding protein expressed on the external surfaces of hepatocytes and breast carcinoma cells [Hembrough, Vasudevan, Allietta, Glass and Gonias (1995) J. Cell Sci. 108, 1071-1082]. In this investigation, we demonstrate that a soluble form of CK 8 is released into the culture medium of breast cancer cell lines. The released CK 8 is in the form of variably sized polymers that bind plasminogen and promote the activation of [Glu1]plasminogen and [Lys78]plasminogen by single-chain tissue-type plasminogen activator (sct-PA). To assess the mechanism by which CK 8 promotes plasminogen activation, CK 8 was purified from rat hepatocytes and immobilized in microtitre plates. Immobilized CK 8 bound 125I-plasminogen and 125I-sct-PA in a specific and saturable manner. The KDs were 160 +/- 40 nM and 250 +/- 48 nM, respectively. Activation of plasminogen bound to immobilized CK 8 was accelerated compared with plasminogen in solution, as determined using a coupled-substrate fluorescence assay and SDS/PAGE. The ability of CK 8 to promote plasminogen activation may be important in the pericellular spaces surrounding breast cancer cells and at the cell surface.Keywords
This publication has 36 references indexed in Scilit:
- A nontetrameric species is the major soluble form of keratin in Xenopus oocytes and rabbit reticulocyte lysates.The Journal of cell biology, 1996
- Dual effect of synthetic plasmin substrates on plasminogen activationBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1995
- INTERMEDIATE FILAMENTS: Structure, Dynamics, Function and DiseaseAnnual Review of Biochemistry, 1994
- Increased expression of cytokeratins 8, 18 and vimentin in the invasion front of mucosal squamous cell carcinomaThe Journal of Pathology, 1993
- Coexpression of Vimentin and Keratins by Human Melanoma Tumor Cells: Correlation With Invasive and Metastatic PotentialJNCI Journal of the National Cancer Institute, 1992
- The plasminogen-plasmin systemProgress in Cardiovascular Diseases, 1991
- Characterization of the binding of plasminogen to fibrin surfaces: The role of carboxy-terminal lysinesBiochemistry, 1991
- Regulation of plasminogen activation by components of the extracellular matrixBiochemistry, 1990
- Characterization of an Extremely Large, Ligand-Induced Conformational Change in PlasminogenScience, 1990
- C‐terminal lysine residues of fibrinogen fragments essential for binding to plasminogenFEBS Letters, 1985