Abstract
Background: Lung cancer stem cells (CSCs) share many characteristics with normal stem cells, such as self-renewal and multipotentiality. High expression of aldehyde dehydrogenase (ALDH) has been detected in many tumors, particularly in the CSC compartment, and it plays an important role in tumor proliferation, metastasis, and drug resistance. CD44 is commonly used as a cell surface marker of cancer stem-like cells in epithelial tumors. The aim of this study was to isolate and analyze cancer stem-like cells from surgically removed specimens to compare lung adenocarcinoma (ADENO) and squamous (SQUAMO) cell carcinoma.Methods: The ALDEFLUOR assay was used to identify and sort ALDHhigh and ALDHlow human lung cancer cells following tissue digestion. Fluorescence-activated cell sorting analysis for CD44 was performed with tumor cells. Quantitative real-time PCR was performed to assess the expression of SOX2 and NANOG as stemness markers. ALDH1A1 expression was additionally determined by immunohistochemistry. Anchorage-independent ALDHhigh cell growth was also evaluated. ALDHhigh ADENO and SQUAMO cells were cultured to analyze spheroid formation.Results: All specimens contained 0.5–12.5% ALDHhigh cells with 3.8–18.9% CD44-positive cells. SOX2 and NANOG relative expression in ALDHhigh compared to ALDHlow cells in ADENO and SQUAMO was analyzed and compared between the histotypes. Immunohistochemistry confirmed the presence of ALDH1A1 in the sections. SOX2 and NANOG were expressed at higher levels in the ALDHhigh subpopulation than in the ALDHlow subpopulation only in ADENO cells, and the opposite result was seen in SQUAMO cells. In vitro functional assays demonstrated that ALDHhigh cells exhibited migration capacity with distinct behaviors between ALDHhigh spheres in ADENO vs. SQUAMO samples.Conclusions: Our results highlight the importance of a better characterization of cancer stem-like cells in ADENO and SQUAMO histotypes. This may suggest new differential approaches for prognostic and therapeutic purposes in patients with non-small-cell lung cancer.
Highlights
Lung cancer stem cells (CSCs) share many characteristics with normal stem cells, such as self-renewal and multipotentiality
The aim of the present study was to identify cancer stem-like cells in primary human lung cancer cells obtained from surgical specimens and to assess the differences and similarities between adenocarcinoma (ADENO) and squamous (SQUAMO) cell carcinoma using a combination of aldehyde dehydrogenase (ALDH) and CD44
Four patients were diagnosed with adenocarcinoma of the lung, and four patients were diagnosed with squamous cell carcinoma (Table 1)
Summary
Lung cancer stem cells (CSCs) share many characteristics with normal stem cells, such as self-renewal and multipotentiality. CD44 is commonly used as a cell surface marker of cancer stem-like cells in epithelial tumors. Chemotherapy drugs cannot differentiate between tumor cells and normal cells while functioning; the treatment-related adverse effects are noticeably strong and feared by patients. It was not until the emergence of targeted therapy based on molecular typing that the survival period of patients with advanced NSCLC was improved to several years. Understanding the role of CSCs in lung cancer may be very important and useful for identifying future targets. Aldehyde dehydrogenase (ALDH) activity is an important functional
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