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Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2006 Mar 01; Vol. 97 (4), pp. 709-23. - Publication Year :
- 2006
-
Abstract
- The expression of CCL20 (MIP-3alpha), which chemoattracts leukocytes to sites of inflammation, has been shown in intestinal epithelial cells (IEC). Aim of this study was to analyze the role of the CCL20 receptor CCR6 in IEC and colorectal cancer (CRC) cells. Expression of CCR6 and CCL20 was analyzed by RT-PCR and immunohistochemistry. Signaling was investigated by Western blotting, proliferation by MTS assays and chemotactic cell migration by wounding assays. The effect of CCL20 on Fas-induced apoptosis was determined by flow cytometry. CCR6 and its ligand CCL20 are expressed in IEC. Moreover, CRC and CRC metastases express CCR6, which is upregulated during IEC differentiation. Stimulation of IEC with CCL20 and proinflammatory stimuli (TNF-alpha, IL-1beta, LPS) significantly upregulates CCL20 mRNA expression. CCL20 expression was significantly increased in inflamed colonic lesions in Crohn's disease and correlated significantly with the IL-8 mRNA expression in these lesions (r = 0.71) but was downregulated in CRC metastases. CCL20 activated Akt, ERK-1/2, and SAPK/JNK MAP kinases and increased IL-8 protein expression. The CCL20 mediated activation of these pathways resulted in a 2.6-fold increase of cell migration (P = 0.001) and in a significant increase of cell proliferation (P < 0.05) but did not influence Fas-induced apoptosis. In conclusion, IEC and CRC express CCL20 and its receptor CCR6. CCL20 expression is increased in intestinal inflammation, while CCR6 is upregulated during cell differentiation. CCR6 mediated signals result in increased IEC migration and proliferation suggesting an important role in intestinal homeostasis and intestinal inflammation by mediating chemotaxis of IEC but also in mediating migration of CRC cells.<br /> (2005 Wiley-Liss, Inc.)
- Subjects :
- Caco-2 Cells
Cell Differentiation physiology
Cell Line, Tumor
Cell Movement physiology
Cell Proliferation
Chemokine CCL20
Chemokines, CC metabolism
Crohn Disease metabolism
Cytokines physiology
Fas Ligand Protein
HCT116 Cells
HT29 Cells
Humans
Inflammation metabolism
Interleukin-8 metabolism
Intestinal Mucosa metabolism
MAP Kinase Kinase 1 physiology
Macrophage Inflammatory Proteins metabolism
Membrane Glycoproteins metabolism
Phosphorylation
Receptors, CCR6
Signal Transduction
Tumor Necrosis Factors metabolism
Colorectal Neoplasms metabolism
MAP Kinase Kinase 4 metabolism
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Proto-Oncogene Proteins c-akt metabolism
Receptors, Chemokine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 97
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16215992
- Full Text :
- https://doi.org/10.1002/jcb.20672