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Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis

Nature Medicine volume 5, pages 803–809 (1999)Cite this article

Abstract

The endoglycosidase heparanase is an important in the degradation of the extracellular matrix by invading cells, notably metastatic tumor cells and migrating leukocytes. Here we report the cDNA sequence of the human platelet enzyme, which encodes a unique protein of 543 amino acids, and the identification of highly homologous sequences in activated mouse T cells and in a highly metastatic rat adenocarcinoma. Furthermore, the expression of heparanase mRNA in rat tumor cells correlates with their metastatic potential. Exhaustive studies have shown only one heparanase sequence, consistent with the idea that this enzyme is the dominant endoglucuronidase in mammalian tissues.

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Figure 1: Nucleotide and deduced amino-acid sequence of human platelet heparanase.
Figure 2: Amino-acid alignment of human, rat and mouse heparanase.
Figure 3: Tissue specificity of human heparanase mRNA.
Figure 4: Genomic Southern blot analysis of the human heparanase gene.
Figure 5: Expression of human heparanase.
Figure 6: Expression of heparanase mRNA in rat metastatic and non metastatic tumor cell lines.

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Acknowledgements

We thank A. Browne, K. Jakobson and E. Pagler for technical assistance and P. Milburn for the amino-acid sequencing. This research was funded by Progen Industries, Brisbane, Australia.

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Authors and Affiliations

  1. Division of Immunology and Cell Biology, John Curtin School of Medical Research, ANU, Canberra, ACT 2601, Australia

    Mark D. Hulett, Craig Freeman, Brenton J. Hamdorf & Christopher R. Parish

  2. Division of Molecular Medicine, John Curtin School of Medical Research, ANU, Canberra, ACT 2601, Australia

    Rohan T. Baker & Matthew J. Harris

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  1. Mark D. Hulett
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Correspondence to Christopher R. Parish.

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Hulett, M., Freeman, C., Hamdorf, B. et al. Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med 5, 803–809 (1999). https://doi.org/10.1038/10525

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