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

Journal Article · Sat Oct 15 00:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.07.006· OSTI ID:20717668

Brand, Stephan ^[1]; Dambacher, Julia ^[1]; Beigel, Florian ^[1]; Olszak, Torsten ^[1]; Diebold, Joachim ^[2]; Otte, Jan-Michel ^[3]; Goeke, Burkhard ^[1]; Eichhorst, Soeren T ^[1]

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1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich (Germany)
2. Institute of Pathology, University-Hospital Munich-Grosshadern, University of Munich (Germany)
3. Department of Medicine I, St. Josef-Hospital, Ruhr-University, Bochum (Germany)

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.

• OSTI ID: 20717668
• Journal Information: Experimental Cell Research, Vol. 310, Issue 1; Other Information: DOI: 10.1016/j.yexcr.2005.07.006; PII: S0014-4827(05)00331-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
APOPTOSIS
CALVES
CELL DIFFERENTIATION
CELL PROLIFERATION
GROWTH FACTORS
LEUKOCYTES
LIGANDS
METASTASES
MICROTUBULES
MONOCLONAL ANTIBODIES
NEOPLASMS
PHOSPHATES
PHOSPHOTRANSFERASES
POLYMERASE CHAIN REACTION
RECEPTORS
TETRAZOLIUM