EMT markers in lung adenocarcinoma pleural effusion spheroid cells

Abstract

Epithelial-to-mesenchymal transition (EMT) is a process in which cells undergo a developmental switch from epithelial to mesenchymal phenotype. This process has been related to embryologic morphogenesis but also to cancer progression and metastasis. The aim of the current study was to investigate the expression of EMT-related markers in adherent and spheroid cell cultures derived from malignant pleural effusions (MPEs) of patients affected by lung adenocarcinoma. On the basis of efficient in vitro propagation, six cases of MPEs were selected and analyzed by immunocytochemistry staining for EMT markers and by RT-PCR for transcription factors known to orchestrate EMT. EMT markers immunostaining showed in spheroids a statistically significant correlation between the loss of E-cadherin immunoreactivity and overexpression of N-cadherin (P < 0.001). Likewise loss of EpCAM epithelial marker was coincident with Vimentin overexpression (P < 0.001). RT-PCR analysis of transcription factors Snail, Slug, and Twist showed a highly variable expression, although a general trend to increase was observed. Importantly, in some selected cases it was possible to establish a precise relationship between spheroid formation, EMT switch and increased upregulation of the marker related to cancer stemness such as ALDH positivity. Therefore, MPE-derived cell cultures, while recapitulating the heterogeneity of lung cancer, are a suitable system to study the mechanisms at the basis of EMT and to understand its relationship with the generation of cancer stem cells.

Long Noncoding RNA-LET Suppresses Tumor Growth and EMT in Lung Adenocarcinoma

“…EMT is a conserved cellular process in which epithelial tumor cell lacks its polarity and transforms into a mesenchymal phenotype [16, 17]. The feature of EMT occurrence is that the epithelial marker E-cadherin is downregulated and mesenchymal marker, like N-cadherin, is upregulated [18, 19]. To demonstrate whether the lncRNA-LET affected EMT, we detected the molecular marker levels of EMT and showed the inhibition of lncRNA-LET on EMT.…”

Slug Is a Predictor of Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients

“…In this context, earlier studies have also reported the role of Slug protein in EMT as a regulator in primary human cancers [26]. Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma [12], breast cancer [9,27], lung cancer [28], bladder cancer [29]. Slug also promotes tumor invasion in lung adenocarcinoma [30].…”

Altered gene products involved in the malignant reprogramming of cancer stem/progenitor cells and multitargeted therapies

“…The EMT phenomenon, which occurs through the tissue and organ morphogenesis and patterning during embryonic development and tissue regeneration and wound healing in adult, is also re-activated during the progression of numerous epithelial cancers such as skin, lung, hepatic, gastrointestinal, colorectal, pancreatic, prostate, ovarian and breast cancers (Alvero et al, 2009; Bao et al, 2011; Cao et al, 2012; Chen et al, 2007; Du et al, 2011; Feldmann et al, 2007; Giarnieri et al, 2013; Hanahan and Weinberg, 2011; Kabashima et al, 2009; Kikuta et al, 2010; Mani et al, 2008; Mimeault and Batra, 2007b; Mimeault and Batra, 2008b; Mimeault and Batra, 2010c; Puhr et al, 2012; Rhim et al, 2012; Shah et al, 2007; Wang et al, 2012b; Wang et al, 2009; Zhang et al, 2012b). Moreover, malignant cells involved in the development of non-epithelial cancers, such as melanomas and brain cancers, can acquire variable degrees of mesenchymal markers and a more invasive ability through an EMT-like process resembling embryonic neural crest invasion program (Bailey et al, 2012; Cheng et al, 2012b; De Bacco F. et al, 2012; Galavotti et al, 2012).…”