Increased migration of colorectal cancer cells induced by TNF-alpha-treated stromal fibroblasts from human liver metasta
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Meeting abstract
Increased migration of colorectal cancer cells induced by TNF-alpha-treated stromal fibroblasts from human liver metastases L Müller*1, J Schumacher1, B Temel1, L von Seggern2, S Tiwari1, H Kalthoff1 and DC Bröring1 Address: 1University Hospital Schleswig-Holstein, Campus Kiel, Molecular Oncology, General and Thoracic Surgery, Kiel, Germany and 2University Hospital Hamburg-Eppendorf, Department of Hepatobiliary Surgery and Solid Organ Transplantation, Hamburg, Germany * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A102
doi:10.1186/1478-811X-7-S1-A102
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.This abstract is available from: http://www.biosignaling.com/content/7/S1/A102 © 2009 Müller et al; licensee BioMed Central Ltd.
Background Inflammation plays key roles in invasion, angiogenesis and metastasis. Given the multifaceted roles of tumornecrosis-factor-alpha (TNF-alpha) in these processes, its effects on the stromal fibroblasts that constitute the desmoplastic stroma in colorectal metastases are of interest.
Methods Primary cultures of cancer-associated stromal fibroblasts (CAFs) were generated from human tissues harvested during hepatic resection. TNF-alpha expression in tissue was examined by immunohistochemistry. Activation of nuclear-factor-kappaB (NF-kappaB) activity was measured by gel mobility shift assay. The effect of TNF-alpha on migratory capacity and gene expression of CAFs was tested in presence/absence of parthenolide, an herbal inhibitor of NF-kappaB. Gene expression in tissues and cell cultures was examined by Northern blot analysis. Protein measurements in the cell culture supernatant were performed with cytometric capture beads.
Results
involved in tumor progression. CAFs that were exposed for 24 hours to TNF-alpha (10 ng/ml) showed a dramatic increased expression of interleukin-6 (IL-6), monocytechemotactic protein-1 (MCP-1) and intercellular cell adhesion molecule-1 (ICAM-1). Increasing concentrations of parthenolide (1, 5, 10 microM) dose-dependently inhibited the activation of NF-kappaB by TNF-alpha exposure for 30 min, as well as the TNF-alpha effect on IL-6 and MCP-1 mRNA and protein expression. Exposure of CAFs with TNF-alpha significantly increased the chemotaxis of HT29 colon carcinoma cells towards these cells in a coculture migration chamber system. This migratory effect activated by paracrine TNF-alpha was inhibited by co-incubation with parthenolide.
Conclusion CAFs are an important target for inflammatory signaling mediated by TNF-alpha/NF-kappaB in the context of tumor-stroma interacti
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