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The heparanase system and tumor metastasis: is heparanase the seed and soil?

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Abstract

Tumor metastasis, the leading cause of cancer patients’ death, is still insufficiently understood. While concepts and mechanisms of tumor metastasis are evolving, it is widely accepted that cancer metastasis is accompanied by orchestrated proteolytic activity executed by array of proteases. While matrix metalloproteinases (MMPs) attracted much attention, other proteases constitute the tumor milieu, of which a large family consists of cysteine proteases named cathepsins. Like MMPs, some cathepsins are often upregulated in cancer and, once secreted or localized to the cell surface, can degrade components of the extracellular matrix. In addition, cathepsin L is held responsible for processing and activation of heparanase, an endo-β-glucuronidase capable of cleaving heparan sulfate side chains of heparan sulfate proteoglycans, activity that is strongly implicated in cell dissemination associated with tumor metastasis, angiogenesis, and inflammation. In this review, we discuss recent progress in heparanase research focusing on heparanase-related molecules namely, cathepsin L and heparanase 2 (Hpa2), a heparanase homolog.

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Acknowledgments

This work was supported by grants from the Israel Science Foundation (593/10); National Cancer Institute, NIH (RO1-CA106456); the Israel Cancer Research Fund (ICRF); and the Ministry of Science and Technology of the State of Israel and the German Cancer Research Center (DKFZ). I. Vlodavsky is a Research Professor at the ICRF. We thank Professor B. Casu (‘Ronzoni’ Institute, Milan, Italy), Dr. C. Pisano and Dr. S. Penco (Sigma-Tau, Rome, Italy) for kindly providing glycol-split species of heparin (compound SST0001) and for their continuous support and collaboration. We gratefully acknowledge the contribution, motivation, and assistance of the research teams in the Cancer and Vascular Biology Research Center of the Rappaport Faculty of Medicine (Technion, Haifa) and the Hadassah-Hebrew University Medical Center (Jerusalem, Israel).

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  1. Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, P. O. Box 9649, Haifa, 31096, Israel

    Gil Arvatz, Itay Shafat, Flonia Levy-Adam, Neta Ilan & Israel Vlodavsky

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  1. Gil Arvatz
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  2. Itay Shafat
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  5. Israel Vlodavsky
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Correspondence to Israel Vlodavsky.

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Arvatz, G., Shafat, I., Levy-Adam, F. et al. The heparanase system and tumor metastasis: is heparanase the seed and soil?. Cancer Metastasis Rev 30, 253–268 (2011). https://doi.org/10.1007/s10555-011-9288-x

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