CXCR7 regulates breast tumor metastasis and angiogenesis in vivo and in vitro

Mol Med Rep. 2018 Mar;17(3):3633-3639. doi: 10.3892/mmr.2017.8286. Epub 2017 Dec 15.

Abstract

The chemokine receptor CXCR7 is regarded as a scavenger receptor for CXCL12, and induces numerous key steps in tumor growth and metastasis. However, the exact molecular mechanism of CXCR7 regulation in breast tumor angiogenesis remains unknown. In the present study, the function of CXCR7 in breast tumors was investigated in vitro and in vivo. The breast cancer MDA‑MB‑231 cell line was used. Pharmacological inhibition of CXCR7 by CCX771 reduced breast tumor invasion, adhesion and metastasis. Furthermore, CXCR7 was essential for the tube formation of HUVECs in vitro, and for blood vessel formation in a Matrigel plug assay in vivo. In addition, vascular endothelial growth factor expression was also decreased in CCX771‑treated MDA‑MB‑231 cells, indicating that CCX771 regulates tumor angiogenesis. The present results indicated that CXCR7 regulated breast cancer metastasis at multiple stages; additional understanding of CXCR7 in tumor environments may develop anti‑metastatic therapy.

Keywords: CXC receptor 7; breast cancer; human umbilical vein endothelial cells; angiogenesis.

MeSH terms

  • Animals
  • Breast Neoplasms / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CXCL12 / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neovascularization, Physiologic / drug effects
  • Receptors, CXCR / antagonists & inhibitors
  • Receptors, CXCR / metabolism*
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • ACKR3 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR
  • Vascular Endothelial Growth Factor A