title: CXCR7-dependent angiogenic mononuclear cell trafficking regulates tumor progression in multiple myeloma.
abstract: The CXCR4/stromal cell-derived factor-1 (SDF-1) axis is essential for cell trafficking and has been shown to regulate tumor progression and metastasis in many tumors including multiple myeloma (MM). A second chemokine receptor for SDF-1, CXCR7 was discovered recently and found on activated endothelial cells. 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 neoangiogenesis. We demonstrate that the CXCR7 inhibitor, POL6926, abrogated trafficking of AMCs to areas of MM tumor progression leading to a significant inhibition of tumor progression. These effects were through regulation of endothelial cells and not through a direct tumor effect, indicating that targeting a bone marrow microenvironmental cell 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.
authors: Abdel Kareem
authors: AK
authors: Azab
authors: Ilyas
authors: I
authors: Sahin
authors: Michele
authors: M
authors: Moschetta
authors: Yuji
authors: Y
authors: Mishima
authors: Nicholas
authors: N
authors: Burwick
authors: Johann
authors: J
authors: Zimmermann
authors: Barbara
authors: B
authors: Romagnoli
authors: Kalpana
authors: K
authors: Patel
authors: Eric
authors: E
authors: Chevalier
authors: Aldo M
authors: AM
authors: Roccaro
authors: Irene M
authors: IM
authors: Ghobria
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology; D045744:Cell Line, Tumor; D018450:Disease Progression; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055153:Stem Cell Niche / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C501896:ACKR3 protein, human; D054387:Receptors, CXCR