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Inhibition of collagenolytic activity relates to quantitative reduction of invasionin vitro in a c-Ha-ras transfected glial cell line

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Abstract

The function of proteases in brain tumor invasion is currently not well established. For tumors of epithelial and fibromatous origin collagenase production can enhance the invasive capacity of cells to penetrate basement membranes. We showed previously that a c-Ha-ras transformed glial cell line (CxT24neo3) invaded hamster brain tissuein vivo. These cells were also capable of invading reconstituted basement membrane and embryonic chick heartsin vitro. Since the histopathology of CxT24neo3 tumors mimics that of glioblastoma multiforme in humans, CxT24neo3 was used as the modelin vitro for this type of brain tumor. Presently, we detected by zymogram analysis a gelatinase that was secreted by CxT24neo3 and that had an apparent molecular mass of 62 kD.

To verify whether gelatinase affected invasionin vitro of these glial cells we determined the efficacy of a substrate specific collagenase inhibitor on invasionin vitro. GM6001 is a synthetic polypeptide that specifically occupies the substrate binding sites of metalloprotease. Since this drug did not show cytotoxicity, its specificity for metalloprotease is a valuable tool to evaluate the physiological function of these enzymes on invasion. We found that treatment of CxT24neo3 with GM6001 reduced the fraction of invading CxT24neo3 cells through reconstituted basement membrane. These data suggest that metalloproteases can stimulate brain tumor invasion.

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Authors and Affiliations

  1. Dept. of Surgery, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY, USA

    E. R. Boghaert

  2. Dept. of Biochemistry, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY, USA

    S. K. Chan, C. Zimmer & T. C. Vanaman

  3. 43 Brassey Ave, 3084, Rosanna, Victoria, Australia

    D. Grobelny

  4. Glycomed Incorporated, 860 Atlantic Ave., 94501, Alameda, CA

    R. E. Galardy

  5. Dept. of Microbiology and Immunology, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY, USA

    S. G. Zimmer

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  1. E. R. Boghaert
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  2. S. K. Chan
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  3. C. Zimmer
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  6. T. C. Vanaman
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  7. S. G. Zimmer
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Boghaert, E.R., Chan, S.K., Zimmer, C. et al. Inhibition of collagenolytic activity relates to quantitative reduction of invasionin vitro in a c-Ha-ras transfected glial cell line. J Neuro-Oncol 21, 141–150 (1994). https://doi.org/10.1007/BF01052898

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