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: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
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| 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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| 245 | 1 | 0 | |a Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis |c Obul R. Bandapalli, Franziska Ehrmann, Volker Ehemann, Matthias Gaida, Stephan Macher-Goeppinger, Moritz Wente, Peter Schirmacher, Karsten Brand |
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| 520 | |a 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. | ||
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