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

Abdel Kareem Azab, Ilyas Sahin, Feda Azab, Michele Moschetta, Yuji Mishima, Nicholas Burwick, Johann Zimmermann, Barbara Romagnoli, Kalpana Patel, Eric Chevalier, Aldo M. Roccaro, Irene M. Ghobrial

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 thatAMCs are circulating in patients withMMand 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.

Original languageEnglish
Pages (from-to)1905-1914
Number of pages10
JournalBlood
Volume124
Issue number12
DOIs
StatePublished - Sep 18 2014

Keywords

  • AMCs home to tumor sites in MM
  • CXCR7 inhibition delayed tumor progression in MM through specific regulation of AMC trafficking but not through a direct tumor effect

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