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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Nevo I,Sagi-Assif O,Meshel T,Ben-Baruch A,Jöhrer K,Greil R,Trejo LE,Kharenko O,Feinmesser M,Yron I,Witz IP

doi

10.1016/j.canlet.2008.07.029

subject

Has Abstract

pub_date

2009-01-08 00:00:00

pages

127-39

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(08)00617-4

journal_volume

273

pub_type

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