Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during

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 o