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

Valentina Masciale; Giulia Grisendi; Federico Banchelli; Roberto D'Amico; Antonino Maiorana; Pamela Sighinolfi; Alessandro Stefani; Uliano Morandi; Massimo Dominici; Beatrice Aramini

doi:10.18632/oncotarget.27568

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

Oncotarget. 2020 Apr 28;11(17):1545-1555. doi: 10.18632/oncotarget.27568.

Authors

Valentina Masciale^{1

2}, Giulia Grisendi^{3

2}, Federico Banchelli^{4

2}, Roberto D'Amico⁴, Antonino Maiorana⁵, Pamela Sighinolfi⁵, Alessandro Stefani¹, Uliano Morandi¹, Massimo Dominici^{3

2}, Beatrice Aramini^{1

2}

Affiliations

¹ Division of Thoracic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
² Co-first/last authors.
³ Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Center of Statistic, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁵ Institute of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

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.

Keywords: cancer stem cells; cancer stem-like cells; immunophenotype; non-small cell lung cancer (NSCLC); target therapy.