PMID: 19148483Jan 17, 2009Paper

Chemokine receptor CXCR4 expression, function, and clinical implications in gastric cancer

International Journal of Oncology
Hyo Jin LeeDeog Yeon Jo

Abstract

The chemokine receptor CXCR4 is associated with the biological behavior of cancer, but few studies have addressed the expression and function of CXCR4 in human gastric cancer and its impact on disease prognosis. We studied the expression of CXCR4 using RT-PCR, Western blotting, flow cytometry, and confocal microscopy in five gastric cancer cell lines. We also examined cell proliferation, migration, and anti-apoptotic activity in response to stromal cell-derived factor (SDF)-1alpha and evaluated SDF-1alpha/CXCR4 signaling pathways. Furthermore, we investigated the correlation between CXCR4 expression and the clinical features of 221 gastric cancer tissue samples. CXCR4 transcripts and proteins were detectable in all five gastric cancer cell lines. However, MKN-28, MKN-45, MKN-74, and SNU16 cells did not express membrane CXCR4. In contrast, KATO III cells expressed membrane CXCR4. In these cells, SDF-1alpha-induced migration was observed and was blocked by AMD3100, a specific inhibitor of CXCR4. SDF-1alpha induced rapid phosphorylation of Erk1/2 MAPK but did not promote phosphorylation of Stat3 or Akt. Gastric cancer tissue samples expressed CXCR4 with variable intensities. Strong CXCR4 expression was significantly associated wit...Continue Reading

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