CD44+/EPCAM+ cells detect a subpopulation of ALDHhigh cells in human non-small cell lung cancer: A chance for targeting cancer stem cells?

Abstract

Objectives: Several studies demonstrated that aldehyde dehydrogenase (ALDH) and CD44 are the most considered cancer stem cells (CSC) markers. However, a comparison between ALDH high cells and CD44+ cells have been previously described with no significant correlation. Indeed, the aim of the present research is to identify a superficial marker able to match with ALDH high cells population in freshly isolated human lung cancer cells. Materials and Methods: This cross-sectional study analyzed the expression of ALDH high/low cells and the positivity for CD44 and epithelium cell adhesion molecule (EPCAM) antigens in surgical lung cancer tissues. The main approach was a cytofluorimetric analysis of ALDH expression and positivity for CD44/EPCAM on primary cell population obtained from 23 patients harboring NSCLC. Results: There was a highly positive correlation between the expressions of ALDH high and CD44+/EPCAM+ cells, with a Pearson's correlation coefficient equal to 0.69 (95% CI 0.39-0.86; P = 0.0002), and Spearman's correlation coefficient equal to 0.52 (P = 0.0124). The average paired difference between the expression of ALDH high and CD44+/EPCAM+ cells was very close to 0, being 0.1% (SD 2.5%); there was no difference between these subpopulations in terms of means (95% CI =-1.0; 1.2%, P = 0.8464). These results highlight a strong similarity between ALDH high and CD44+/ EPCAM+ cells. Conclusions: Our study is the first attempt which identifies a high correlation between the ALDH high and the CD44+/EPCAM+ cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells.

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

“…More recently, Masciale et al [ 28 ] have identified and isolated lung CSCs from primary tumors based on ALDH expression, demonstrating their high capacity to form in vitro tumor spheres. Additionally, the results in adenocarcinoma and squamous cell carcinoma of the lung showed that the cells successfully grew for three weeks in a serum-free medium, forming spheres and overexpressing stemness genes, i.e., SOX2 and NANOG [ 28 , 29 , 30 , 31 ].…”

New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

“…Recently, Masciale et al. have suggested that there is a subpopulation of cells CD44+/EpCAM+ with a high correlation with ALDH high cell populations ( 49 ) which were previously shown to be cancer stem cells in NSCLC patients ( 48 ). A marker like ALDH for cancer stem cells has also been identified and described by many scientists ( 50 – 52 ).…”

Cancer stem cells and macrophages: molecular connections and future perspectives against cancer

“…These identification markers may be subjected to genetic modifications and identify specific CSCs subpopulations with different molecular characteristics. For example, the upregulated ATP-binding cassette (ABC) transporter G subfamily (ABCG), absence or presence of mutated NOTCH1, or different isotypes as observed for CD44v [ 33 , 52 – 56 ].…”

“…Different markers for CSCs have been studied in the last recent decades, and scientists tried have attempted to improve the identification of this better this subpopulation by using a double or triple marker [ 15 , 32 , 33 , 65 – 70 ]. Masciale et al reported a novel subpopulation of cells expressing CD44+/epithelial cell adhesion molecule (EpCAM + ) that was positively correlated with ALDH+ cells [ 33 ]. They compared two similar CSC populations.…”

“…The CSC theory was the most impressive in solid tumors in the absence of another approach to distinguish between a tumorigenic and non-tumorigenic cell due to similarity in their kinetic properties and because cancer is hierarchically organized [ 21 ]. One of the main obstacles to proving the CSC model is the difficulty in identification and isolation of these cells [ 7 , 33 , 91 ]. In fact, scientists first tried to define a CSC model using xenografts for the testing and identification of markers, and isolation of tumor-initiating cells [ 91 , 92 ].…”