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Cathepsin L antisense oligonucleotides in a human osteosarcoma cell line: Effects on the invasive phenotype

Cancer Gene Therapy volume 8, pages 522–528 (2001)Cite this article

Abstract

Alterations in cathepsin L expression and trafficking have been associated with the progression and metastasis of several tumor entities. In the present study, we examined the effects of various cathepsin L antisense (as) phosphorothioate oligonucleotides on both the expression of cathepsin L and the invasive potential of the human osteosarcoma cell line MNNG/HOS. Seven oligonucleotides of 20-bp length each and one random control oligonucleotide were chosen to block cathepsin L expression. Northern blot analysis demonstrated a significant reduction in cathepsin L mRNA expression by the six antisense oligonucleotides at a concentration of 10 μM. Cathepsin L protein expression was reduced significantly (50–85%) by the antisense oligonucleotides, as compared with the controls. Adhesion to matrices of collagen I and matrigel was not affected. In in vitro motility and invasion assays performed in uncoated and precoated transwell chambers, the ability of cells to migrate through the filters was inhibited by 35–75% using antisense oligonucleotides. The random control did not show any inhibitory effect. These data demonstrate that in MNNG/HOS cells cathepsin L influences cellular malignancy by promoting migration and basement membrane degradation. Cancer Gene Therapy (2001) 8, 522–528

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (SFB387). We gratefully acknowledge the excellent technical assistance of Doreen Gärtner. The authors thank Bernd Wüsthoff for help in preparing the manuscript.

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Authors and Affiliations

  1. Department of Pathology, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, Magdeburg, 39120, Germany

    Sabine Krueger, Udo Kellner & Albert Roessner

  2. Institute of Immunology, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, Magdeburg, 39120, Germany

    Frank Buehling

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  1. Sabine Krueger
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  2. Udo Kellner
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  3. Frank Buehling
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  4. Albert Roessner
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Correspondence to Sabine Krueger.

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Krueger, S., Kellner, U., Buehling, F. et al. Cathepsin L antisense oligonucleotides in a human osteosarcoma cell line: Effects on the invasive phenotype. Cancer Gene Ther 8, 522–528 (2001). https://doi.org/10.1038/sj.cgt.7700341

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