Muehlbauer, Marcus and Ringel, Susanne and Hartmann, Arndt and Lallinger, Gertrud and Weiss, Thomas S. and Gaebele, Erwin and Wuensch, Peter H. and Schoelmerich, Juergen and Hellerbrand, Claus (2005) Lack of association between the functional CX3CR1 polymorphism V249I and hepatocellular carcinoma. ONCOLOGY REPORTS, 13 (5). pp. 957-963. ISSN 1021-335X,
Full text not available from this repository. (Request a copy)Abstract
Chemokine production by cancer cells constitutes a duality. Leukocyte recruitment under the pressure of chemokines may be beneficial for the host or for the tumor. Recently, the chemokine fractalkine and its receptor CX3CR1 have been shown to be expressed in hepatocytes in vivo and in a human hepatocarcinoma cell line in vitro. Therefore, the aim of this study was to analyze the expression of CX3CR1 in hepatocellular carcinoma (HCC) in vivo and to investigate the prevalence of the genetic CX3CR1 polymorphism V2491 in HCC patients since this polymorphism has been associated with reduced number of fractalkine binding sites, reduced cell-cell adhesion and decreased signaling and chemotaxis. Genotyping was performed in 183 patients with histologically proven HCC and 99 healthy controls by RFLP-analysis. The frequency of the individual genotypes was similar in HCC patients and controls. The V2491 polymorphism revealed no association with tumor grade and stage, the presence of extrahepatic metastasis or the degree of fibrosis in non-tumorous tissue. In addition to genotyping, CX3CR1 mRNA expression was analyzed by quantitative PCR in 9 HCC specimens and in 6 cases in corresponding non-tumorous liver tissues. CX3CR1 mRNA expression levels in HCC showed high variation between individual patients. Similarly, expression in HCC compared to non-tumorous liver varied, from strong downregulation to remarkable upregulation. CX3CR1 mRNA expression levels showed no correlation to the V2491 polymorphism. In summary, these results suggest that the pathophysiological role of individual chernokines in carcinogenesis may vary and that the functional CX3CR1 polymorphism V2491 is no genetic risk factor for HCC. However, additional independent studies in HCC patients with different ethnic background will be needed to confirm the present study and to elucidate the functional role of CX3CR1 and its polymorphism V2491 in chronic liver disease and hepatocarcinogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MONOCYTE CHEMOATTRACTANT PROTEIN-1; SMOOTH-MUSCLE-CELLS; RECEPTOR CX3CR1; GENETIC POLYMORPHISMS; EPITHELIAL-CELLS; LIVER-DISEASE; TNF-ALPHA; FRACTALKINE; EXPRESSION; CHEMOKINE; CX3CR1; fractalkine; chemokines; risk factor; hepatocellular carcinoma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 May 2021 10:53 |
| Last Modified: | 14 May 2021 10:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36200 |
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