CXCR7-dependent angiogenic mononuclear cells trafficking regulates tumor progression in multiple myeloma

Angiogenesis is a hallmark of progression in multiple myeloma (MM), and many studies have shown that angiogenesis should be considered as a therapeutic target in MM. The CXCR4/SDF-1 axis is essential for cell trafficking and has been shown to regulate tumor progression and metastasis in many tumors including MM. A second chemokine receptor for SDF-1, CXCR7 was discovered recently and is expressed on activated endothelial cells. In this study, we examined the role of CXCR7 in angiogenic mononuclear cells (AMCs) trafficking in MM. Our data demonstrate that AMCs are circulating in patients with MM and in vivo studies show that they specifically home to areas of MM tumor growth. CXCR7 expression is important for regulating trafficking and homing of AMCs into areas of MM tumor growth and neo-angiogenesis. In vitro and in vivo studies confirmed that the CXCR7 inhibitor, POL6926 abrogated trafficking of AMCs to areas of MM tumor progression leading to a significant inhibition of tumor progression in MM. These effects were through regulation of endothelial cells and not through a direct tumor effect. These studies indicate that targeting a bone marrow microenvironmental cell and not direct inhibition of the tumor cells can lead to a delay in MM tumor progression. In conclusion, our studies demonstrate that CXCR7 may play an important role in the regulation of tumor progression in MM through an indirect effect on the recruitment of AMCs to areas of MM tumor growth in the bone marrow niche. For personal use only. on October 28, 2017. by guest www.bloodjournal.org From