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Front. Oncol. | doi: 10.3389/fonc.2019.00331

Leukocyte heparanase: a double-edged sword in tumor progression

  • 1La Trobe Institute for Molecular Science, La Trobe University, Australia
  • 2Hudson Institute of Medical Research, Australia

Heparanase is a β-D-endoglucuronidase that cleaves heparan sulfate, a complex glycosaminoglycan found ubiquitously throughout mammalian cells and tissues. Heparanase has been strongly associated with important pathological processes including inflammatory disease and tumor metastasis, through its ability to promote various cellular functions such as cell migration, invasion, adhesion and cytokine release. A number of cell types express heparanase including leukocytes, cells of the vasculature as well as tumor cells. However, the relative contribution of heparanase from these different cell sources to these processes is poorly defined. It is now well established that the immune system plays a critical role in shaping tumor progression. Intriguingly, leukocyte-derived heparanase has been shown to either assist or impede tumor progression, depending on the setting. This review covers our current knowledge of heparanase in immune regulation of tumor progression, as well as the potential applications and implications of exploiting or inhibiting heparanase in cancer therapy.

Keywords: Heparanase, Leukocytes, Macrophages, Natural Killer cells, Immunotherapy, tumor progression

Received: 26 Feb 2019; Accepted: 11 Apr 2019.

Edited by:

Giuliana Cassinelli, National Tumor Institute (Italy), Italy

Reviewed by:

Lukas Martin, University Hospital RWTH Aachen, Germany
Mauro S. Pavao, Federal University of Rio de Janeiro, Brazil  

Copyright: © 2019 Mayfosh, Baschuk and Hulett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mark D. Hulett, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia,