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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی O-16: The Chemokine Receptor CXCR4 is Expressed on Human Gastric Adenocarcinoma and is Downregulated by Thalidomide
چکیده انگلیسی مقاله Stromal derived factor-1 (SDF-1 or CXCL12), a member of the alpha chemokines (CXC) and the ligand for the CXCR4 receptor, has been shown in the past to be an effective chemoattractant for various CXCR4-expressing cells. SDF-1 is secreted by stromal and endothelial cells in bone marrow, lung, skeletal muscle, liver, kidney and brain. It is therefore important for metastasis of cancer cells to these organs. Recent studies have shown that CXCR4 plays an important role in cancer development and tumor growth, apoptosis inhibition, angiogenesis promotion, cellular proliferation, invasion and cancer metastasis in many cancers. Herein, we studied the expression of CXCR4 on gastric samples from patients with gastric adenocarcinoma as well as human gastric carcinoma epithelial cell line, AGS, by employing RTPCR and immunehistochemistry (IHC) techniques. RT-PCR data show that CXCR4 is highly expressed on AGS cells. This was confirmed by IHC as CXCR4 is detected in cell membrane and cytoplasm of AGS cell line. More importantly, we found that CXCR4 is strongly expressed on primary gastric cancer cells from patients, but not on normal gastric cells from normal individuals (as detected by IHC staining). Thalidomide is an old drug which has recently shown to inhibit of CXCR4 and vascular endothelial growth factor (VEGF) expression in multiple myeloma cells. This prompted us to investigate the role of thalidomide on CXCR4 expression in AGS. We demonstrate that thalidomide downregulates CXCR4 in AGS cell line. In conclusion, we present evidence that CXCR4 is expressed on gastric carcinoma and thus CXCR4 may be a suitable marker for diagnosis of gastric cancer. In addition, for the first time, we show that thalidomide might a potential approach for targeting of CXCR4 in gastric cancer. Further investigations are ongoing in the laboratory to confirm this finding in vitro.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1524
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