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Heparanase and the hallmarks of cancer
journal contributionposted on 2021-01-07, 02:31 authored by Krishnath Jayatilleke, Mark HulettMark Hulett
© 2020, The Author(s).
Heparanase is the only mammalian enzyme that cleaves heparan sulphate, an important component of the extracellular matrix. This leads to the remodelling of the extracellular matrix, whilst liberating growth factors and cytokines bound to heparan sulphate. This in turn promotes both physiological and pathological processes such as angiogenesis, immune cell migration, inflammation, wound healing and metastasis. Furthermore, heparanase exhibits non-enzymatic actions in cell signalling and in regulating gene expression. Cancer is underpinned by key characteristic features that promote malignant growth and disease progression, collectively termed the ‘hallmarks of cancer’. Essentially, all cancers examined to date have been reported to overexpress heparanase, leading to enhanced tumour growth and metastasis with concomitant poor patient survival. With its multiple roles within the tumour microenvironment, heparanase has been demonstrated to regulate each of these hallmark features, in turn highlighting the need for heparanase-targeted therapies. However, recent discoveries which demonstrated that heparanase can also regulate vital anti-tumour mechanisms have cast doubt on this approach. This review will explore the myriad ways by which heparanase functions as a key regulator of the hallmarks of cancer and will highlight its role as a major component within the tumour microenvironment. The dual role of heparanase within the tumour microenvironment, however, emphasises the need for further investigation into defining its precise mechanism of action in different cancer settings.
Australian National Health and Medical Research Council Project Grant APP471424.
JournalJournal of Translational Medicine
Pagination25p. (p. 1-25)
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
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Science & TechnologyLife Sciences & BiomedicineMedicine, Research & ExperimentalResearch & Experimental MedicineHeparanaseCancerHallmarks of cancerExtracellular matrixTumour microenvironmentFIBROBLAST-GROWTH-FACTORTUMOR-ENDOTHELIAL-CELLSEPITHELIAL-MESENCHYMAL TRANSITIONHYPOXIA-INDUCIBLE FACTORSSUBENDOTHELIAL EXTRACELLULAR-MATRIXMACROPHAGES PROMOTE ANGIOGENESISGA-BINDING-PROTEINREGULATORY T-CELLSTGF-BETABREAST-CANCERImmunology