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A CD166 Negative Subpopulation of Pancreatic Cancer Cells Has Strong Invasive and Migratory Activity
Kenji Fujiwara*1, Kenoki Ohuchida1, Koji Shindo2,1, Daiki Eguchi1, Shingo Kozono1, Takao Ohtsuka1, Shunichi Takahata1, Shinichi Aishima2, Kazuhiro Mizumoto1, Masao Tanaka1 1Departments of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 2Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
BACKGROUND: CD166 expression is correlated with prognosis in several cancers. However, its significance in pancreatic cancer is not clear. The aim of this study is to clarify the significance of CD166 expression in pancreatic cancer. METHODS: We performed flow cytometry to analyze expression of CD166 in pancreatic cancer cell lines. We also analyzed the functional differences between CD166+ and CD166- cells using invasion, migration and proliferation assays. We performed immunohistochemistry to investigate CD166 expression in surgically resected pancreatic cancer tissues. RESULTS: In flow cytometry, CD166 was expressed in pancreatic cancer cells in wide range (0-99.5%). In invasion assay, the invasiveness of CD166- cells was greater than that of CD166+ cancer cells (p<0.05). .In migration assay, the migratory activity of CD166- cells was greater than that of CD166+ cancer cells (p<0.05). In proliferation assay, there was no significant difference between CD166+ pancreatic cancer cells and CD166- cells. The analysis of real-time quantitative RT-PCR revealed that epithelial-mesenchymal transition activator Zeb1 mRNA was over-expressed in CD166- cells (p<0.001 compared with that in CD166 + cells). In immunohistochemistry, there was no significant difference in prognosis between CD166 high staining group (15 patients; 48.4%) and CD166 low staining group (16 patients; 51.6%). CONCLUSION: Our findings suggest that CD166- cells exhibit more aggressive behavior and activation of Zeb1 may play a role in this behavior, although further investigation is needed.
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