title: Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Dental Hygiene, China Medical University, Taichung, Taiwan.
authors: Su-Feng
authors: SF
authors: Chen
authors: Yaoh-Shiang
authors: YS
authors: Lin
authors: Shu-Wen
authors: SW
authors: Jao
authors: Yun-Ching
authors: YC
authors: Chang
authors: Chia-Lin
authors: CL
authors: Liu
authors: Yu-Ju
authors: YJ
authors: Lin
authors: Shin
authors: S
authors: Nieh
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000378:metabolism / Q000473:pathology*; D018874:Spheroids, Cellular / Q000378:metabolism; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human
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