Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer

AbstractThe high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. Using quantitative PCR, gene express…

Differential expression of tumorspheres in CSC-markers and signaling pathways from non-small cell lung cancer.

e23276Background: Chemoresistance, tumor progression and metastasis have made of lung cancer the first cause of death cancer-related worldwide. Cancer stem cells (CSCs) are small subpopulations of ...

EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale.

EpCAM, known as an epithelial cell adhesion molecule, plays an essential role in cell adhesion, migration, metastasis and cell signalling. Rather than acting as an apoptosis antagonist, it induces cellular proliferation that impacts the cell cycle, and as a signalling transducer it uses and enhances the Wnt pathway, which is significantly relevant in cell renewal and cancer. EpCAM has become a marker of circulating tumour cells (CTCs) in lung cancer due to its specificity, and its high and stable expression level. Recent findings have allowed us to relearn and discover EpCAM again as a CSCs marker by demonstrating its role in human epithelial cancer progression. In line with this, the focus…

Oral microbiome in Proliferative Verrucous Leukoplakia exhibits loss of diversity and enrichment of pathogens.

Abstract Objectives Oral microbiome plays an important role in oral diseases. Among them, proliferative verrucous leucoplakia (PVL) is an uncommon form of progressive multifocal leukoplakia with a worryingly rate of malignant transformation. Here, we aimed to characterize the oral microbiome of PVL patients and compare it with those of healthy controls. Material and methods Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their microbial communities. The sequence of the V3-V4 region of 16S rRNA gene was used as the taxonomic basis to estimate and analyze the composition and diversity of bacterial populations present in the samples. Results O…

Abstract 4424: Cancer stem cells-related microRNAs have prognostic implications in non-small cell lung cancer

Abstract Background: Lung cancer stem cells (CSCs) are a small population of stem-like cells that remains largely unknown. MicroRNAs (miRNAs) regulation of CSCs gene expression has been reported, constituting a promising therapeutic target. The aim of this study was to isolate and analyze differential expression of a set of miRNAs in tumorspheres from lung cancer cell lines and tumor tissue from resectable non-small cell lung cancer (NSCLC) patients and to determine the prognostic implications of these miRNAs in a cohort of resected-NSCLC patients. Methods: Lung CSC-related miRNAs (miR-145-5p, miR-188-5p, miR-218-5p, miR-34a-5p, miR-21-5p and miR-125a-5p) were analyzed in cells from seven N…

An expression signature characterizes cancer stem cells from lung adenocarcinoma patients

Abstract 3354: Characterization of lung tumorspheres by gene expression and flow cytometry: differential expression in CSC-related markers and signaling pathways

Abstract Chemoresistance, progression and metastasis have made of lung cancer the first cause of cancer mortality. These features were linked to a subpopulation of cells, named cancer stem cells (CSCs), which remain largely unknown. The aim of this study was to isolate and characterize CSCs from lung cancer cell-lines and tumor-tissue from resectable non-small cell lung cancer (NSCLC). Methods: Tumor cells from resected NSCLC and cell lines (H1650, H1993, A549, and PC9) were grown in monolayer and as spheroids. RTqPCR was performed to analyze the mRNA expression of CSCs-related genes: CSC-markers (EPCAM1, ALDH1A1, CD166, ABCG2, CD44, CD133); pluripotency genes (KLF4, OCT4, NANOG, SOX2, MYC,…

Lung tumorspheres as a platform for testing new therapeutic strategies in lung cancer.

e23177Background: Resistance to treatment is one of the causes influencing the high mortality of lung cancer. This feature seems to be dependent of a small subset of special characteristics of self...

Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer

Simple Summary Non-small cell lung cancer (NSCLC) is the second most commonly diagnosed cancer and the leading cause of cancer-related death worldwide. Clinical decision-making depends on the histological classification; however, tissue biopsy is frequently not technically feasible due to tumor location or limited tissue samples. Therefore, we propose to find clinical, molecular and histological biomarkers using a minimally invasive approach based on the analysis of the cargo of the blood extracellular vesicles. Exosomes are membranous vesicles present in several biological fluids, which carry biological information to distant tissues, regulating several tumor processes. This study aims to …

Abstract 1918: Gene characterization of lung-tumorspheres for their usage as an in vitro screening platform for testing new therapeutic strategies

Abstract Background: Lung cancer features like treatment resistance or tumor relapse have been linked to cancer stem cells (CSCs), a population of cells with self-renewal properties, and the ability to grow forming tumorspheres in non-adherent conditions. The aim of this study was to isolate and characterize tumorspheres from lung cancer cell lines and tumor tissue from resectable non-small cell lung cancer (NSCLC) patients and to use them as an in vitro platform for drug screening. Methods: This study was performed on cells from seven NSCLC tumor samples and five cell lines (H1650, H1993, H1395, A549 and PC9) grown in monolayer and as spheroids. The expression of 60 genes, including CSC-ma…

Analysis of the Gut Microbiota: An Emerging Source of Biomarkers for Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer

Simple Summary The immune checkpoint blockade (ICB), and concretely the blockade of the PD1/PDL1 axis, has opened up a new standard of treatment for non-small cell lung cancer (NSCLC). However, despite substantial advances in clinical care, many patients still remain refractory to these therapies. Biomarkers such as PD-L1 expression and tumor mutational burden have been associated with ICB efficacy, but the mechanisms underlying variable responses are not yet fully understood. Recently, the differential composition of the gut microbiota was studied as one of the variables accounting for interpatient heterogeneity in ICB responses. To better understand the potential role of the gut microbiot…

New generation of cancer stem cells inhibitors in non-small cell lung cancer.

e20545Background: Lung cancer is the commonest tumor worldwide of which the most frequent type is non-small cell lung cancer (NSCLC) that represents a large proportion of cancer deaths and is chara...

3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study

Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study, different three-dimensional (3D) printing platforms were used to establish novel 3D cell cultures enriched in CSCs from non-small cell lung cancer (NSCLC) patients and cell lines. Rigid scaffolds with an elevated compressive modulus and uniform pores and channels were produced using different filaments. Hydrogel-based scaffolds were printed with…

Differentially methylated genes in proliferative verrucous leukoplakia reveal potential malignant biomarkers for oral squamous cell carcinoma

Objectives: To explore the pathophysiology of proliferative verrucous leucoplakia (PVL) through a methylated DNA immunoprecipitation and high-throughput sequencing (MeDIP-seq) case-control study. Materials and & nbsp; Methods: Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their epigenetic patterns. Network biology methods and integrative analyses of MeDIP-seq and RNAseq data were applied to investigate functional relations among differentially methylated genes (DMGs). The value of selected genes as malignant biomarkers was evaluated in a large cohort of oral squamous cell carcinoma (OSCC) patients from TCGA.& nbsp; Results: A total of 464…

A gene expression signature to characterize human lung adenocarcinoma cancer stem cells.

e20547Background: Treatment resistance is linked to cancer stem cells (CSCs), a highly tumorigenic subpopulation of cells with the ability to grow as spheres in non-adherent conditions. The aim of ...