The involvement of the fractalkine receptor in the transmigration of neuroblastoma cells through bone-marrow endothelial cells

Ido Nevo, Orit Sagi-Assif, Tsipi Meshel, Adit Ben-Baruch, Karin Jöhrer, Richard Greil, Leonor E.Leider Trejo, Oleg Kharenko, Meora Feinmesser, Ilana Yron, Isaac P. Witz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Transendothelial migration (TEM) of tumor cells is a crucial step in metastasis formation. The prevailing paradigm is that the mechanism underlying TEM of tumor cells is similar to that of leukocytes involving adhesion molecules and chemokines. Fractalkine (CX3CL1) is a unique membrane-bound chemokine that functions also as an adhesion molecule. CX3CL1 can be cleaved to a soluble fragment, capable of attracting fractalkine receptor (CX3CR1)-expressing cells. In the present study, we asked if CX3CR1 is involved in the TEM of neuroblastoma cells. We demonstrated that biologically functional CX3CR1 is expressed by several neuroblastoma cell lines. Most importantly, CX3CR1-expressing neuroblastoma cells were stimulated by CX3CL1 to transmigrate through human bone-marrow endothelial cells. A dose dependent phosphorylation of ERK1/2 and AKT was induced in CX3CR1-expressing neuroblastoma cells by soluble CX3CL1. In addition to CX3CR1, neuroblastoma cells also express the CX3CL1 ligand. Membrane CX3CL1 expression was downregulated and the shedding of soluble CX3CL1 was upregulated by PKC activation. Taken together, the results of this study indicate that CX3CR1 plays a functional role in transmigration of neuroblastoma cells through bone-marrow endothelium. These results led us to hypothesize that the CX3CR1-CX3CL1 axis takes part in bone-marrow metastasis of neuroblastoma.

Original languageEnglish
Pages (from-to)127-139
Number of pages13
JournalCancer Letters
Volume273
Issue number1
DOIs
StatePublished - 8 Jan 2009

Keywords

  • CX3CL1
  • CX3CR1
  • Fractalkine
  • Human bone-marrow endothelial cells
  • Neuroblastoma

Fingerprint

Dive into the research topics of 'The involvement of the fractalkine receptor in the transmigration of neuroblastoma cells through bone-marrow endothelial cells'. Together they form a unique fingerprint.

Cite this