gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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

Meeting Abstract

Suche in Medline nach

  • Claudia Rubie - Allgemein,- Visceral,- und Gefäßchirurgie, Labor für Allgemein,- Visceral,- und Gefäßchirurgie, Homburg/Saar
  • Vilma Frick - Allgemein,- Visceral,- und Gefäßchirurgie, Labor für Allgemein,- Visceral,- und Gefäßchirurgie, Homburg/Saar
  • Pirus Ghadjar - Inselspital, Universität Bern, Radio-Onkologie, Bern
  • Martin K. Schilling - Allgemein,- Visceral,- und Gefäßchirurgie, Labor für Allgemein,- Visceral,- und Gefäßchirurgie, Homburg a.d. Saar

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch332

DOI: 10.3205/11dgch332, URN: urn:nbn:de:0183-11dgch3327

Veröffentlicht: 20. Mai 2011

© 2011 Rubie et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: 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.

Materials and 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 (Caco2, 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 Caco2 cells. CXCL12 stimulation had no impact on Caco2 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).

Conclusion: 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.