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CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation.

Abstract：

:Colorectal cancer (CRC) is characterized by a distinct metastatic pattern resembling chemokine-induced leukocyte trafficking. This prompted us to investigate expression, signal transduction and specific functions of the chemokine receptor CXCR4 in CRC cells and metastases. Using RT-PCR analysis and Western blotting, we demonstrated CXCR4 and CXCL12 expression in CRC and CRC metastases. Cell differentiation increases CXCL12 mRNA levels. Moreover, CXCR4 and its ligand are inversely expressed in CRC cell lines with high CXCR4 and low or not detectable CXCL12 expression. CXCL12 activates ERK-1/2, SAPK/JNK kinases, Akt and matrix metalloproteinase-9. These CXCL12-induced signals mediate reorganization of the actin cytoskeleton resulting in increased cancer cell migration and invasion. Moreover, CXCL12 increases vascular endothelial growth factor (VEGF) expression and cell proliferation but has no effect on CRC apoptosis. Therefore, the CXCL12/CXCR4 system is an important mediator of invasion and metastasis of CXCR4 expressing CRC cells.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Brand S,Dambacher J,Beigel F,Olszak T,Diebold J,Otte JM,Göke B,Eichhorst ST

doi

10.1016/j.yexcr.2005.07.006

keywords:

subject

Has Abstract

pub_date

2005-10-15 00:00:00

pages

117-30

issue

1

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(05)00331-9

journal_volume

310

pub_type

杂志文章

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