title: Down-regulation of CXCL1 inhibits tumor growth in colorectal liver metastasis.
abstract: 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.
authors: Department of General Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
authors: Obul R
authors: OR
authors: Bandapalli
authors: Franziska
authors: F
authors: Ehrmann
authors: Volker
authors: V
authors: Ehemann
authors: Matthias
authors: M
authors: Gaida
authors: Stephan
authors: S
authors: Macher-Goeppinger
authors: Moritz
authors: M
authors: Wente
authors: Peter
authors: P
authors: Schirmacher
authors: Karsten
authors: K
authors: Brand
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D054360:Chemokine CXCL1 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt