Heparanase promotes myeloma stemness and in vivo tumorigenesis.

Heparanase promotes myeloma stemness and in vivo tumorigenesis. Matrix Biol. 2019 Dec 05;: Authors: Tripathi K, Ramani VC, Bandari SK, Amin R, Brown EE, Ritchie JP, Stewart MD, Sanderson RD Abstract Heparanase is known to enhance the progression of many cancer types and is associated with poor patient prognosis. We recently reported that after patients with multiple myeloma were treated with high dose chemotherapy, the tumor cells that emerged upon relapse expressed a much higher level of heparanase than was present prior to therapy. Because tumor cells having stemness properties are thought to seed tumor relapse, we investigated whether heparanase had a role in promoting myeloma stemness. When plated at low density and grown in serum-free conditions that support survival and expansion of stem-like cells, myeloma cells expressing a low level of heparanase formed tumor spheroids poorly. In contrast, cells expressing a high level of heparanase formed significantly more and larger spheroids than did the heparanase low cells. Importantly, heparanase-low expressing cells exhibited plasticity and were induced to exhibit stemness properties when exposed to recombinant heparanase or to exosomes that contained a high level of heparanase cargo. The spheroid-forming heparanase-high cells had elevated expression of GLI1, SOX2 and ALDH1A1, three genes known to be associated with myeloma stemness. Inhibitors that block the heparan sulfate degradin...
Source: Matrix Biology - Category: Molecular Biology Authors: Tags: Matrix Biol Source Type: research