CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

Rubie, Claudia; Frick, Vilma O; Ghadjar, Pirus; Wagner, Mathias; Justinger, Christoph; Faust, Sabrina K; Vicinus, Benjamin; Gräber, Stefan; Kollmar, Otto; Schilling, Martin K (2011). CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells. Journal of translational medicine, 9, p. 22. London: BioMed Central 10.1186/1479-5876-9-22

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Background

Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition.
Methods

Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies.
Results

In CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05).
Conclusions

CXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology

UniBE Contributor:

Ghadjar, Pirus

ISSN:

1479-5876

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

01 Jan 2015 18:31

Publisher DOI:

10.1186/1479-5876-9-22

PubMed ID:

21349176

Web of Science ID:

000288092000001

BORIS DOI:

10.7892/boris.1052

URI:

https://boris.unibe.ch/id/eprint/1052 (FactScience: 201774)

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