Abstract
Introduction. Previous studies have shown that stromal-derived factor-1 (CXCL12) and its receptor, CXCR4, play a crucial role in metastasis of various tumors. Similarly, it has been cleared that CXCR4 is expressed on the cell surface of gastric cancers. However, nuclear expression of CXCR4 and its clinical importance have not been yet studied. Materials and Methods. Herein, we studied the expression of CXCR4 in gastric samples from patients with gastric adenocarcinoma as well as human gastric carcinoma cell line, AGS, by employing RT-PCR, immunohistochemistry, and flow cytometry techniques. Results. RT-PCR data showed that CXCR4 is highly expressed on AGS cells. This was confirmed by IHC and FACS as CXCR4 was detected on cell membrane, in cytoplasm, and in nucleus of AGS cells. Moreover, we found that both cytoplasmic and nuclear CXCR4 are strongly expressed in primary gastric cancer and the cytoplasmic pattern of CXCR4 tends to be associated with a shorter overall survival than nuclear staining. In conclusion, we present evidence for the first time that both cytoplasmic and nuclear expression of CXCR4 are detectable in gastric cancer tissues. However, the role of both cytoplasmic and nuclear CXCR4 needs to be further elucidated.
Highlights
Previous studies have shown that stromal-derived factor-1 (CXCL12) and its receptor, CXCR4, play a crucial role in metastasis of various tumors
We examined CXCR4 expression in gastric cancer cell line, AGS, by using reverse transcription-polymerase chain reaction (RT-PCR) and found that CXCR4 transcripts are highly expressed in this cell line (Figure 1(a))
Our flow cytometry data indicate that CXCR4 is expressed at a low level on AGS cell surface
Summary
Previous studies have shown that stromal-derived factor-1 (CXCL12) and its receptor, CXCR4, play a crucial role in metastasis of various tumors. We present evidence for the first time that both cytoplasmic and nuclear expression of CXCR4 are detectable in gastric cancer tissues. Many studies have shown that metastasis of cancer cells from primary site resembles trafficking of normal cells which is governed by chemokines and their receptors, growth factors, adhesion molecules, and matrix metalloproteinases [3]. Accumulating evidence indicates that chemokines are involved in cell proliferation and chemoresistance of many tumors such as gastric cancer, breast cancer, and leukemia [5,6,7]. CXCR4 is a G-coupled receptor which binds its ligand, stromal-derived factor-1 (CXCL12), and plays a crucial role in retention of hematopoietic stem cells (HSCs) within the bone marrow [8]. CXCR4 expression has been shown to be overexpressed in over 23 human cancers including breast, ovarian, melanoma, prostate, and gastric cancers [4]
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