Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation.

Article Details

Citation

Copy to clipboard

Hembrough TA, Kralovich KR, Li L, Gonias SL

Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation.

Biochem J. 1996 Aug 1;317 ( Pt 3):763-9.

PubMed ID

8760360 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tenecteplase	Keratin, type II cytoskeletal 8	Protein	Humans	Unknown	Not Available	Details