CD271⁺ subpopulation of pancreatic stellate cells correlates with prognosis of pancreatic cancer and is regulated by interaction with cancer cells.
CD271⁺ subpopulation of pancreatic stellate cells correlates with prognosis of pancreatic cancer and is regulated by interaction with cancer cells.
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DOI：
10.1371/journal.pone.0052682
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Fujiwara K;Ohuchida K;Mizumoto K;Shindo K;Eguchi D;Kozono S;Ikenaga N;Ohtsuka T;Takahata S;Aishima S;Tanaka M
胰腺星状细胞（PSCs）在胰腺癌的侵袭行为中起着至关重要的作用。虽然PSC的异质性已被确定，但功能差异仍不清楚。我们表征了人胰腺癌中的CD 271 + PSC。对31例正常胰腺组织和105例胰腺导管腺癌（PDAC）进行CD 271免疫组化。我们进行了流式细胞术和定量RT-PCR，并评估了从胰腺组织中分离的PSC中CD 271的表达以及与癌细胞共培养的PSC中CD 271表达的变化。我们还研究了CD 271在SCID小鼠异种移植模型中的表达模式。在免疫组化分析中，正常胰腺组织和PDAC中胰腺基质中CD 271高染色率分别为2/31（6.5%）和29/105（27.6%）（p = 0.0069）。 在PDAC中，CD 271+基质细胞经常在肿瘤的边缘而不是中心观察到。间质CD 271高表达与良好预后相关（p = 0.0040）。 流式细胞术分析显示PSC中CD 271阳性率为0- 2.1%。定量RT-PCR分析显示，与胰腺癌细胞共培养后，PSC中CD 271 mRNA的表达增加。然而，CD 271 mRNA表达水平在短暂升高后随后下降。此外，通过Matrigel向胰腺癌细胞迁移的PSC中CD 271 mRNA表达降低。在异种移植模型中，CD 271 + PSC存在于肿瘤边缘/外周，而在肿瘤核心中不存在。总之，CD 271在胰腺肿瘤周围的PSC中表达，但在肿瘤中心不表达，并且在与胰腺癌细胞长时间共培养或向胰腺癌细胞移动后表达降低。这些结果表明，CD 271 + PSC出现在胰腺癌发生的早期阶段，CD 271表达与PDAC患者的预后良好显著相关。
Pancreatic stellate cells (PSCs) play a crucial role in the aggressive behavior of pancreatic cancer. Although heterogeneity of PSCs has been identified, the functional differences remain unclear. We characterized CD271+ PSCs in human pancreatic cancer. Immunohistochemistry for CD271 was performed for 31 normal pancreatic tissues and 105 pancreatic ductal adenocarcinomas (PDACs). We performed flow cytometry and quantitative RT-PCR, and assessed CD271 expression in PSCs isolated from pancreatic tissues and the changes in CD271 expression in PSCs cocultured with cancer cells. We also investigated the pattern of CD271 expression in a SCID mouse xenograft model. In the immunohistochemical analyses, the CD271-high staining rates in pancreatic stroma in normal pancreatic tissues and PDACs were 2/31 (6.5%) and 29/105 (27.6%), respectively (p = 0.0069). In PDACs, CD271+ stromal cells were frequently observed on the edge rather than the center of the tumors. Stromal CD271 high expression was associated with a good prognosis (p = 0.0040). Flow cytometric analyses demonstrated CD271-positive rates in PSCs were 0–2.1%. Quantitative RT-PCR analyses revealed that CD271 mRNA expression was increased in PSCs after coculture with pancreatic cancer cells. However, the level of CD271 mRNA expression subsequently decreased after the transient increase. Furthermore, CD271 mRNA expression was decreased in PSCs migrating toward pancreatic cancer cells through Matrigel. In the xenograft model, CD271+ PSCs were present at tumor margins/periphery and were absent in the tumor core. In conclusion, CD271 was expressed in PSCs around pancreatic tumors, but not in the center of the tumors, and expression decreased after long coculture with pancreatic cancer cells or after movement toward pancreatic cancer cells. These findings suggest that CD271+ PSCs appear at the early stage of pancreatic carcinogenesis and that CD271 expression is significantly correlated with a better prognosis in patients with PDAC.
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影响因子：
11.5
作者：
Armstrong, T;Packham, G;Iredale, JP
通讯作者：
Iredale, JP
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29.4
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Bachem, MG;Schneider, E;Adler, G
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Adler, G
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Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
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Logsdon, Craig D.
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影响因子：
29.4
作者：
Bachem, MG;Sch端nemann, M;Adler, G
通讯作者：
Adler, G