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Expression of gelatinise/type IV collagenase in tumor necrosis correlates with cell detachment and tumor invasion

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We have previously observed that acellular extracts from necrotic areas (NE) of the non-metastatic murine mammary adenocarcinoma M3, enhancein vitro cell detachment and spontaneous lung metastases. In the present study, using different proteinase inhibitors along with NE, only the calcium chelator EDTA could significantly abrogate the enhanced cell detachment from M3 produced by NE. The typical cleavage products of type IV collagenase were detected inside the tumor necrotic area, mainly in association with necrobiotic cells, as evaluated by Western blot analysis and immunohistochemical assays. Zymography revealed the presence of 72- and 92-kDa gelatinise/type IV collagenase in NE. Moreover, NE increased thein vitro invasive ability of cultured M3 cells. The use of specific antibodies against both 72- and 92-kDa type IV collagenases in the invasion assay showed that only the latter was able to revert the enhanced invasiveness to the baseline. It can be concluded that tumor necrosis is an important source of gelatinise/type IV collagenase, mainly in its 92 kDa form, and plays a major role in tumor invasion.

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Authors and Affiliations

  1. HHEMA, Academia Nacional de Medicina, Argentina

    R. Daniel Bonfil, Paula A. Medina, Alberto Lazarowski, M. Fernanda Lucero Gritti, Roberto P. Meiss & Oscar D. Bustuoabad

  2. Fundación de Investigación del Cáncer, Argentina

    R. Daniel Bonfil, Paula A. Medina & M. Fernanda Lucero Gritti

  3. Fundación de Investigación del Cáncer, F. D. Roosevelt 2408 1° “C”, 1428, Buenos Aires, Argentina

    Daniel E. Gómez & Eduardo Farias

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  1. R. Daniel Bonfil
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  2. Paula A. Medina
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  3. Daniel E. Gómez
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  4. Eduardo Farias
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  5. Alberto Lazarowski
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  6. M. Fernanda Lucero Gritti
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  7. Roberto P. Meiss
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  8. Oscar D. Bustuoabad
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Daniel Bonfil, R., Medina, P.A., Gómez, D.E. et al. Expression of gelatinise/type IV collagenase in tumor necrosis correlates with cell detachment and tumor invasion. Clin Exp Metast 10, 211–220 (1992). https://doi.org/10.1007/BF00132753

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  • DOI: https://doi.org/10.1007/BF00132753

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