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Heparanase enzyme in chronic inflammatory bowel disease and colon cancer

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Abstract

Heparanase is the sole mammalian endoglycosidase that cleaves heparan sulfate, the key polysaccharide of the extracellular matrix and basement membranes. Enzymatic cleavage of heparan sulfate profoundly affects a variety of physiological and pathological processes, including morphogenesis, neovascularization, inflammation, and tumorigenesis. Critical involvement of heparanase in colorectal tumor progression and metastatic spread is widely documented; however, until recently a role for heparanase in the initiation of colon carcinoma remained underappreciated. Interestingly, the emerging data that link heparanase to chronic inflammatory bowel conditions, also suggest contribution of the enzyme to colonic tumor initiation, at least in the setting of colitis-associated cancer. Highly coordinated interplay between intestinal heparanase and immune cells (i.e., macrophages) preserves chronic inflammatory conditions and creates a tumor-promoting microenvironment. Here we review the action of heparanase in colon tumorigenesis and discuss recent findings, pointing to a role for heparanase in sustaining immune cell-epithelial crosstalk that underlies intestinal inflammation and the associated cancer.

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Acknowledgments

We thank Prof. Israel Vlodavsky (Cancer and Vascular Biology Research Center, the Rappaport Faculty of Medicine, Technion, Haifa, Israel) for his continuous help and collaboration. This work was supported by grants from the German-Israel Research Foundation (GIF), Israel Science Foundation (grant 593/10), and Chief Scientist Office—Israeli Ministry of Health.

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  1. Tumor Biology Research Unit, Department of Oncology, Sharett Institute, Hadassah-Hebrew University Medical Center, 91120, Jerusalem, Israel

    Esther Hermano, Immanuel Lerner & Michael Elkin

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  1. Esther Hermano
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  2. Immanuel Lerner
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  3. Michael Elkin
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Correspondence to Michael Elkin.

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E. Hermano and I. Lerner contributed equally to this work.

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Hermano, E., Lerner, I. & Elkin, M. Heparanase enzyme in chronic inflammatory bowel disease and colon cancer. Cell. Mol. Life Sci. 69, 2501–2513 (2012). https://doi.org/10.1007/s00018-012-0930-8

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