3627

CXCL10

C7|IFI10|INP10|IP-10|SCYB10|crg-2|gIP-10|mob-1;chemokine (C-X-C motif) ligand 10;CXCL10;chemokine (C-X-C motif) ligand 10

10 kDa interferon gamma-induced protein|C-X-C motif chemokine 10|gamma IP10|gamma-IP10|interferon-inducible cytokine IP-10|protein 10 from interferon (gamma)-induced cell line|small inducible cytokine subfamily B (Cys-X-Cys), member 10|small-inducible cyt

4q21

protein-coding

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 proliferation of CAG, U266 and RPMI-8266 myeloma cells. Similarly, CXCL10 attenuated the proliferation of human umbilical vein endothelial cells, implying that CXCL10 exhibits anti-angiogenic capacity. Strikingly, development of tumor xenografts produced by CAG-heparanase cells overexpressing CXCL10 was markedly reduced compared with control cells. Moreover, tumor growth was significantly attenuated in mice inoculated with human or mouse myeloma cells and treated with CXCL10-Ig fusion protein, indicating that CXCL10 functions as a potent anti-myeloma cytokine.