Migratory Activity of CD105+ Pancreatic Cancer Cells Is Strongly Enhanced by Pancreatic Stellate Cells
Migratory Activity of CD105+ Pancreatic Cancer Cells Is Strongly Enhanced by Pancreatic Stellate Cells
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DOI：
10.1097/mpa.0b013e318293e7bd
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发表时间：
2013-11
期刊：
影响因子：
2.9
通讯作者：
K. Fujiwara;K. Ohuchida;T. Ohtsuka;K. Mizumoto;Koji Shindo;Naoki Ikenaga;Lin Cui;S. Takahata
中科院分区：
文献类型：
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作者：
K. Fujiwara;K. Ohuchida;T. Ohtsuka;K. Mizumoto;Koji Shindo;Naoki Ikenaga;Lin Cui;S. Takahata
目的 CD105 表达与多种癌症的预后相关。然而，其在胰腺癌中的意义尚不清楚。方法 我们分析了切除的胰腺癌组织和胰腺癌细胞系中的 CD105 表达，使用定量 RT-PCR 和迁移测定比较了 CD105+ 和 CD105− 细胞的特性，并评估了 CD105+ 细胞和胰腺星状细胞 (PSC) 之间的关系。结果免疫组化显示胰腺癌组织中CD105的表达频率高于正常组织（分别为8%和0%）。流式细胞术检测发现胰腺癌细胞中表达CD105，而正常胰腺导管上皮细胞中检测到微弱的CD105表达。定量RT-PCR显示CD105+细胞中E-cadherin mRNA表达受到抑制，vimentin mRNA过表达（P < 0.05）。在与 PSC 共培养中，CD105+ 癌细胞的迁移显着增强（大于 CD105− 细胞）（P < 0.05）。 CD105 表达与临床病理特征或 Kaplan-Meier 生存分析无关。结论 上皮标记物的抑制和间质标记物的过度表达表明在 CD105+ 胰腺癌细胞中诱导了上皮-间质转化。 PSC 强烈增强 CD105+ 胰腺癌细胞迁移，表明这些细胞在胰腺癌微环境中发挥作用。
Objectives CD105 expression correlates with prognosis for several cancers. However, its significance in pancreatic cancer is unclear. Methods We analyzed CD105 expression in resected pancreatic cancer tissue and pancreatic cancer cell lines, compared the properties of CD105+ and CD105− cells using quantitative RT-PCR and migration assays, and evaluated the relationship between CD105+ cells and pancreatic stellate cells (PSCs). Results Immunohistochemistry showed that the frequency of CD105 expression was higher in pancreatic cancer than that in normal tissue (8% vs 0%, respectively). In flow cytometry, CD105 was expressed in pancreatic cancer cells, whereas weak CD105 expression was detected in normal pancreatic ductal epithelial cells. Quantitative RT-PCR showed that E-cadherin mRNA expression was suppressed and vimentin mRNA was overexpressed in CD105+ cells (P < 0.05). Migration of CD105+ cancer cells was strongly enhanced (more than that of CD105− cells) in coculture with PSCs (P < 0.05). CD105 expression did not correlate to clinicopathologic characteristics or the Kaplan-Meier survival analysis. Conclusions Suppression of an epithelial marker and overexpression of a mesenchymal marker suggest that epithelial-mesenchymal transition is induced in CD105+ pancreatic cancer cells. CD105+ pancreatic cancer cell migration is strongly enhanced by PSCs, suggesting that these cells play a role in the pancreatic cancer microenvironment.