LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus?

Abstract

BackgroundInvestigation of the expression of an intestinal stem cell marker in esophageal adenocarcinomas (EAC) with and without Barrett's Esophagus (BE), with respect to a cancer stem cell (CSC) hypothesis.Materials and methodsExpression of a putative intestinal stem cell marker LgR5 was analyzed in esophageal cancer specimen (n = 70: 41 EAC with BE, 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC) and in the adenocarcinoma cell line OE-33. Ki-67 and Cdx-2 were co-labelled with LgR5 in double staining experiments. Immunhistochemical expression results were confirmed by RT-PCR and correlated with tumor stage and five-year survival rates.ResultsLgR5was found expressed in 35 of 41 (85%) EAC with BE and in 16 of 19 (81%) EAC without BE. By contrast, LgR5 was not found to be expressed in ESCC. Quantification of immunolabeling showed 15% LgR5+ cells in EAC with BE, 32% LgR5+ cells in adjacent BE and 13% in EAC without BE. Immunofluorescence double staining experiments with LgR5 and Ki-67 revealed a subpopulation (~5%) of proliferating LgR+/Ki-67+ cells. On mRNA-level, expression of LgR5 was higher in BE in comparison to EAC (p = 0.0159). High levels of LgR5 expression in BE associated EAC were associated with poorer survival in univariate analysis.ConclusionThe stem cell marker LgR5 is expressed in EAC, irrespective of association with BE, and appears to have negative impact on survival. The subset of proliferating LgR5+ cells (<5%) might resemble rapidly cycling CSCs, which needs to be substantiated in further investigations.

Apoptosis resistance-related ABCB5 and DNaseX (Apo10) expression in oral carcinogenesis

“…In contrast, the clonal selection model of multi-step carcinogenesis implies that a random solitary cell undergoes malignant transformation, accumulates multiple mutations and subsequently acquires a survival advantage, which leads to clonal selection [17,18]. Our results of significant up-regulation of ABCB5 in precursor lesions and down-regulation in OSCC are in concordance to results in other solid tumor entities investigating CSC markers during carcinogenesis in our previous study [19]. However, it is important to note that the two models are not mutually exclusive, as CSCs themselves may undergo clonal evolution, as already shown for leukemia cells [20,21].…”

Expression and clinical significance of SALL4 and LGR5 in patients with lung cancer

“…In a previous study, LGR5 was found to be expressed in 35 out of 41 (85%) esophageal adenocarcinoma (EAC) tissues with Barrett's esophagus (BE) and in 16 out of 19 (81%) EAC tissues without BE. By contrast, LGR5 was not found to be expressed in esophageal squamous cell carcinoma tissues (25). In another study, RT-quantitative PCR analysis was performed on a panel of representative cancer cell lines derived from various organs, consisting of 11 colon cancer, 5 human hepatocellular carcinoma, 10 ovarian cancer and 11 lung cancer cell lines (26).…”

Cancer Stem Cells and Stemness Markers in Oral Squamous Cell Carcinomas

“…Recent reports have associated this marker with head and neck carcinoma as it has been detected in the oral tissue of mice as well as in the side populations of HNSCC cell lines (Haegebarth and Clevers, 2009;Rahden et al, 2011).…”

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