Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade.
Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade.
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DOI：
10.1371/journal.pone.0054659
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nieh S
中科院分区：
文献类型：
--
作者：
Chen SF;Lin YS;Jao SW;Chang YC;Liu CL;Lin YJ;Nieh S
转移发生在一系列不连续的步骤中，包括侵袭、血管生成、淋巴血管间隙渗透和继发性肿瘤的建立。恶性胸腔积液（MPE）是一种肿瘤转移，通常是肺腺癌患者预后不良的标志，尽管其潜在机制受到的关注少于其他类型的转移。本研究的目的是确认MPE中的癌症干细胞（CSC）是否通过上皮-间质转化（EMT）、失巢凋亡和微环境中的适应而促成"转移级联"。通过免疫组织化学染色，使用CSC代表性标志物（CD133、Nanog和OCT-4）和EMT相关标志物（E-钙粘蛋白和波形蛋白），分析了20例原发性腺癌患者MPE样本的肺组织和相应细胞块。分析这些变量与临床病理参数之间的相关性。研究了8例MPE的原代培养物，以表征CSC的特性，包括标记物表达、球体形成和分化。20例MPE细胞块的CSC代表性标志物的表达是相当多样化的，并且在15%至90%的范围内变化。与原发性肺肿瘤组织中的表达相比，在浸润前沿和MPE中发现CSC代表性标志物的表达更强，EMT相关标志物的改变。OCT-4在MPE中的表达与远处转移和分期显著相关，与患者生存率呈负相关。原代培养证实MPE中的CSC特性。8例MPE中有5例产生了足够的细胞簇，除了球体形成和分化和转移能力外，还显示了CSC标志物的可变表达。这项初步研究提供了一个更好的理解转移级联。建立MPE模型将进一步了解CSC在转移中的作用，并可能解释MPE患者的高治疗失败率。
Metastasis occurs in a series of discrete steps involving invasion, angiogenesis, lymphovascular space permeation, and establishment of secondary tumors. Malignant pleural effusion (MPE), a type of tumor metastasis, is usually a poor prognostic sign for patients with pulmonary adenocarcinoma, although its underlying mechanism has received less attention than other types of metastases have. The objective of the current study was to confirm whether cancer stem cells (CSCs) in MPE contribute to the “metastatic cascade” through the epithelial – mesenchymal transition (EMT), anoikis, and adaptation in the microenvironment. Pulmonary tissue and corresponding cell blocks of MPE samples from 20 patients with primary adenocarcinoma were analyzed by immunohistochemical staining with CSC-representative markers (CD133, Nanog, and OCT-4) and EMT-associated markers (E-cadherin and vimentin). Correlations between these variables and clinico-pathological parameters were analyzed. Primary cultures from eight cases of MPE were investigated to characterize the CSC properties, including marker expression, sphere formation, and differentiation. Expressions of CSC-representative markers for 20 cases of MPE cell blocks were quite diverse and variable ranging from 15% to 90%. Stronger expression of CSC-representative markers and alteration of EMT-associated markers were found at the invasive fronts and in MPEs compared with the expression in primary pulmonary tumor tissues. The expression of OCT-4 in MPEs significantly related to distant metastasis and stage, as well as inversely correlated with patient survival. Primary cultures confirmed the CSC properties in MPE. Five of eight cases of MPE yielded adequate cell clusters, which also showed variable expressions of CSC markers in addition to sphere formation and the ability for differentiation and metastasis. This pilot study offers a better understanding of the metastatic cascade. Establishing a model of MPE will provide further insight into the role of CSCs in metastasis and may explain the high therapeutic failure rates for patients with MPE.
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影响因子：
3.7
作者：
Chen SF;Chang YC;Nieh S;Liu CL;Yang CY;Lin YS
通讯作者：
Lin YS
影响因子：
--
作者：
Bertrand K
通讯作者：
Bertrand K
影响因子：
7.3
作者：
Horst, David;Scheel, Silvio K.;Jung, Andreas
通讯作者：
Jung, Andreas
影响因子：
2.8
作者：
Hackbarth, Jennifer S.;Murata, Kazunori;Algeciras-Schimnich, Alicia
通讯作者：
Algeciras-Schimnich, Alicia
影响因子：
21.3
作者：
Avizienyte, E;Wyke, AW;Frame, MC
通讯作者：
Frame, MC