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Walker 256 cancer cells secrete tissue inhibitor of metalloproteinase-free metalloproteinase-9

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Abstract

Walker 256 (W256) cancer cells, developed as ascites in rats, in response to endogenous unidentified stimuli, secrete a gelatinase of apparent molecular mass of 94 kDa, immunologically homologous to the zymogen of matrix metalloproteinase-9 (proMMP-9). After treatment with the activating agent 4-aminophenylmercuric acetate (APMA), affinity-purified W256 gelatinase is converted to a final processed form of 66 kDa in a similar fashion to TIMP-free human proMMP-9. It is demonstrated that although being capable of binding TIMP-1, W256 proMMP-9 is secreted from W256 cells in TIMP-free forms (monomers or oligomers). Moreover, using biochemical and immunological methods, it is established that the W256 cells do not express or secrete TIMP-1 protein, although RT-PCR analysis indicated low-level TIMP-1 mRNA expression. W256 cancer cells displayed high metastatic ability in rats that may be attributed in part to secretion of TIMP-free proMMP-9.

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We thank Dr. Stanley Zucker for critical review and advice on the manuscript.

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  1. Maria Pavlaki

    Present address: Foundation for Biomedical Research of the Academy of Athens, Athens, Greece

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  1. Laboratory of Biochemistry, Department of Chemistry, School of Natural Sciences, University of Patras, Patras, 265 04, Greece

    Maria Pavlaki, Anna Niarakis & Alexios J. Aletras

  2. Department of Pharmacology, School of Medicine, University of Patras, Patras, Greece

    Eleftheria Giannopoulou

  3. Department of Pathology, University Hospital of Patras, School of Medicine, University of Patras, Patras, Greece

    Panagiota Ravazoula

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  1. Maria Pavlaki
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Pavlaki, M., Giannopoulou, E., Niarakis, A. et al. Walker 256 cancer cells secrete tissue inhibitor of metalloproteinase-free metalloproteinase-9. Mol Cell Biochem 328, 189–199 (2009). https://doi.org/10.1007/s11010-009-0089-2

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