Chronic Colitis & Colitis-Associated Cancer: Heparanase an Important Target

The enzyme heparanase is responsible for release and activation of various growth-promoting molecules, and degradation of non-cellular components in tissue matrices. It is found to be over expressed and activated in patients with Ulcerative Colitis and to significantly increase the incidence of severity of colitis associated colonic tumors.

In the setting of wound healing, traumatic tissue disruption destroys the cellular elements of the tissue, but at the same time initiates the heparanase-mediated healing process. In the setting of tissue engraftment (e.g., organ transplantation), heparanase is responsible for releasing and activating pro-angiogenic molecules, which promote the formation of new blood vessels and their growth into the newly transplanted organ.

Chronic colitis and the associated colon tumorigenesis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is closely associated with colon cancer. Using histological specimens from patients with UC, we found that heparanase is constantly over-expressed and activated during the course of the disease, both in the active and inactive phases of inflammation. Employing a mouse model of colitis-associated cancer in which the gene that encodes heparanase was over-expressed, we demonstrated that heparanase markedly increased the incidence and severity of colitis-associated colonic tumors. This finding positions heparanase as an important physiological determinant in inflammation-driven colon carcinoma, and attests that inhibiting heparanase activity and/or expression is a promising strategy to disrupt the vicious cycle that drives chronic colitis and the associated tumorigenesis.

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Inventor - Professor Israel Vlodavsky