Heparanase enhances myeloma progression via CXCL10 downregulation.

ABSTRACT: In order to explore the mechanism(s) underlying the pro-tumorigenic capacity of heparanase, we established an inducible Tet-on system. Heparanase expression was markedly increased following addition of doxycycline (Dox) to the culture medium of CAG human myeloma cells infected with the inducible heparanase gene construct, resulting in increased colony number and size in soft agar. Moreover, tumor xenografts produced by CAG-heparanase cells were markedly increased in mice supplemented with Dox in their drinking water compared with control mice maintained without Dox. Consistently, we found that heparanase induction is associated with decreased levels of CXCL10, suggesting that this chemokine exerts tumor-suppressor properties in myeloma. Indeed, recombinant CXCL10 attenuated the proliferati

SUBMITTER: Barash U 

PROVIDER: S-EPMC4185261 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature