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Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis

As part of ongoing studies to obtain a global picture of invasion related events in colorectal liver metastases, here, we report our findings on gene expression of the pro-angiogenic subgroup of chemokines, the CXCL-ELR+ chemokines. Apart from their pro-angiogenic and chemoattractant function, these...

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Main Authors: Bandapalli, Obul Reddy (Author) , Ehrmann, Franziska (Author) , Ehemann, Volker (Author) , Gaida, Matthias (Author) , Macher-Göppinger, Stephan (Author) , Wente, Moritz N. (Author) , Schirmacher, Peter (Author) , Brand, Karsten (Author)
Format: Article (Journal)
Language:English
Published: 2012
In: Cytokine
Year: 2012, Volume: 57, Issue: 1, Pages: 46-53
ISSN:1096-0023
DOI:10.1016/j.cyto.2011.10.019
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.cyto.2011.10.019
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1043466611008064
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Author Notes:Obul R. Bandapalli, Franziska Ehrmann, Volker Ehemann, Matthias Gaida, Stephan Macher-Goeppinger, Moritz Wente, Peter Schirmacher, Karsten Brand
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Summary:As part of ongoing studies to obtain a global picture of invasion related events in colorectal liver metastases, here, we report our findings on gene expression of the pro-angiogenic subgroup of chemokines, the CXCL-ELR+ chemokines. Apart from their pro-angiogenic and chemoattractant function, these chemokines appear to also contribute to tumor cell transformation, growth and invasion. In our nude mouse model of colorectal liver metastases, we found CXCL1,2,3,5 and 8 (IL-8) to be up-regulated in the tumor cells of the invasion front as compared to the tumor cells in the inner parts of the tumor. ShRNA mediated down-regulation of the most prominently up-regulated group member, CXCL1/gro-alpha resulted in inhibition of cell viability, invasion and proliferation. In vivo, down-regulation of CXCL1 resulted in a nearly complete prevention of tumor growth in nude mice. Mechanistically, auto-regulatory mechanisms involving NF-kappaB and Akt appear to be involved in pro-tumorigenic functions of CXCL1.
Item Description:Available online 29 November 2011
Gesehen am 26.09.2018
Physical Description:Online Resource
ISSN:1096-0023
DOI:10.1016/j.cyto.2011.10.019

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