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Lymphoma

Triggering of T-cell leukemia and dissemination of T-cell lymphoma in MMP-9-deficient mice

Leukemia volume 21, pages 2506–2511 (2007)Cite this article

Abstract

Previous studies have shown that high levels of MMP-9 can be detected in the serum of patients with various lymphoid malignancies and in leukemia/lymphoma culture supernatants. Indeed, aggressive forms of lymphoma constitutively produce MMP-9 and its elevated levels in the serum or in tissues correlate with advanced stage and poor patient survival. In vitro, MMP-9, which is also produced by the host peritumoral cells in response to the presence of tumors, plays an important role in migration of tumor cells through artificial basement membranes or endothelial cells. In this study, using MMP-9-deficient mice, we show that absence of MMP-9 does not prevent the development of primary T-cell leukemia. Furthermore, MMP-9-deficient cell lines retained their tumorigenic potential, as shown by their ability to induce thymic lymphoma in young syngeneic wild-type animals. In addition, these MMP-9-deficient tumor cells disseminate in normal mice, or mice that are deficient for MMP-9, indicating that tumor growth and dissemination can occur in total absence of MMP-9. These results show for the first time than lymphoma growth can occur in total absence of MMP-9 and have consequences for therapy of invasive cancers with inhibitors of MMPs.

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Acknowledgements

We thank Doris Legault and Diane Tremblay for their excellent technical support, and Dr Edouard F Potworowski for critical reading of the manuscript. YSP is a scholar of the Fonds de la Recherche en Santé du Québec (FRSQ). MD and CVT were supported by studentships from the Fonds de la Recherche FRSQ. JSR is supported by a studentship from the Fondation Armand-Frappier. This work was supported by the Canadian Institute for Health Research and the National Cancer Institute of Canada (YSP) and the Belgian Foundation against Cancer, the Fund for Scientific Research of Flanders and the Geconcerteerde OnderzoeksActies (2006-2010) (GO).

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Authors and Affiliations

  1. INRS-Institut Armand-Frappier, University of Québec, Laval, Québec, Canada

    J-S Roy, M Demers & Y St-Pierre

  2. Department of Chemistry Biology, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada

    C Van Themsche

  3. Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium

    G Opdenakker

  4. Laboratory for Molecular Immunology, German Cancer Research Center, Heidelberg, Germany

    B Arnold

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  1. J-S Roy
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  2. C Van Themsche
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  4. G Opdenakker
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  6. Y St-Pierre
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Correspondence to Y St-Pierre.

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Roy, JS., Van Themsche, C., Demers, M. et al. Triggering of T-cell leukemia and dissemination of T-cell lymphoma in MMP-9-deficient mice. Leukemia 21, 2506–2511 (2007). https://doi.org/10.1038/sj.leu.2404936

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