Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling

Cancer Lett. 2011 Dec 15;312(1):1-10. doi: 10.1016/j.canlet.2011.06.028. Epub 2011 Jul 7.

Abstract

Bone marrow metastasis is frequently observed in patients with high-risk neuroblastoma. Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastasis through secreting stromal cell-derived factor-1 (SDF-1). Here we investigated neuroblastoma cell behaviors under the influence of MSCs and explored the function of SDF-1 signaling during metastasis. Neuroblastoma expressed both of the SDF-1 receptors CXCR4 and CXCR7. shRNA knockdown showed that these receptors were responsible for the migration of neuroblastoma towards MSCs. CXCR4 also supported neuroblastoma invasion. These effects could be effectively blocked by AMD3100, a potent SDF-1 antagonist. Our study suggests that MSCs are important for neuroblastoma metastasis via the secretion of SDF-1 and that such effect can be inhibited by AMD3100 or shRNA knockdown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Chemotaxis / physiology
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Neoplasm Metastasis
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Receptors, CXCR / biosynthesis*
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism
  • Receptors, CXCR4 / biosynthesis*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Signal Transduction

Substances

  • ACKR3 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • RNA, Small Interfering
  • Receptors, CXCR
  • Receptors, CXCR4