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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 ALDHhigh/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 ALDHhigh 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 ALDHhigh 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 ALDHhigh and CD44+/EPCAM+ cells. CONCLUSIONS:Our study is the first attempt which identifies a high correlation between the ALDHhigh and the CD44+/EPCAM+ cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells.

SUBMITTER: Masciale V

PROVIDER: S-EPMC7197447 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Masciale Valentina V Grisendi Giulia G Banchelli Federico F D'Amico Roberto R Maiorana Antonino A Sighinolfi Pamela P Stefani Alessandro A Morandi Uliano U Dominici Massimo M Aramini Beatrice B

Oncotarget 20200428 17

<h4>Objectives</h4>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.<h4>Materials and methods</h4>This cross-sectional study an ...[more]

PMID: 32391123

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Project description:BackgroundHuman prostate basal cells expressing alpha-6 integrin (CD49f(Hi)) and/or CD44 form prostaspheres in vitro. This functional trait is often correlated with stem/progenitor (S/P) activity, including the ability to self-renew and induce differentiated tubules in vivo. Antigenic profiles that distinguish tubule-initiating prostate stem cells (SCs) from progenitor cells (PCs) and mature luminal cells (LCs) with less regenerative potential are unknown.Methodology/principle findingsProstasphere assays and RT-PCR analysis was performed following FACS separation of total benign prostate cells based upon combinations of Epcam, CD44, and/or CD49f expression. Epithelial cell fractions were isolated, including Epcam(+)CD44(+) and Epcam+CD44+CD49f(Hi) basal cells that formed abundant spheres. When non-sphere-forming Epcam(+)CD44(-) cells were fractionated based upon CD49f expression, a distinct subpopulation (Epcam(+)CD44(-)CD49f(Hi)) was identified that possessed a basal profile similar to Epcam(+)CD44(+)CD49f(Hi) sphere-forming cells (p63(+)AR(Lo)PSA(-)). Evaluation of tubule induction capability of fractionated cells was performed, in vivo, via a fully humanized prostate tissue regeneration assay. Non-sphere-forming Epcam(+)CD44(-) cells induced significantly more prostate tubular structures than Epcam(+)CD44(+) sphere-forming cells. Further fractionation based upon CD49f co-expression identified Epcam(+)CD44(-)CD49f(Hi) (non-sphere-forming) basal cells with significantly increased tubule induction activity compared to Epcam(+)CD44(-)CD49f(Lo) (true) luminal cells.Conclusions/significanceOur data delineates antigenic profiles that functionally distinguish human prostate epithelial subpopulations, including putative SCs that display superior tubule initiation capability and induce differentiated ductal/acini structures, sphere-forming PCs with relatively decreased tubule initiation activity, and terminally differentiated LCs that lack both sphere-forming and tubule-initiation activity. The results clearly demonstrate that sphere-forming ability is not predictive of tubule-initiation activity. The subpopulations identified are of interest because they may play distinct roles as cells of origin in the development of prostatic diseases, including cancer.

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

Publications

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

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