Introduction Cartilage endplate (CEP) degeneration is usually accompanied by loss of cellularity, and this loss may be a crucial key factor in initiation and development of degenerative disc disease. The study of cell types in degenerated CEP could help in understanding CEP etiopathogenesis, and may help in devising new treatments, especially if the presence of progenitor cells could be demonstrated. The aim of this study was to determine if progenitor cells existed in degenerated human CEP. Materials and methods Cells isolated from CEP were cultured in a three-dimensional agarose suspension to screen for proliferative cell clusters. Cell clusters were then expanded in vitro and the populations were analyzed for colony forming unit, immunophenotype, multilineage induction, and expression of stem cell-related genes. Results The presence of progenitor cells in degenerated human CEP is indicated by the results of CFU, immunophenotype, multilineage induction, and expression of stem cell-related genes. Conclusions We believe that this is the first study which has conclusively shown the presence of progenitor cells in degenerated CEP. The finding of this study may influence the clinical management of degenerative disc disorder.
Mesenchymal stem cells (MSCs) are recruited into the tumour microenvironment and promote tumour growth and metastasis. Tumour microenvironment-induced autophagy is considered to suppress primary tumour formation by impairing migration and invasion. Whether these recruited MSCs regulate tumour autophagy and whether autophagy affects tumour growth are controversial. Our data showed that MSCs promote autophagy activation, reactive oxygen species production, and epithelial-mesenchymal transition (EMT) as well as increased migration and invasion in A549 cells. Decreased expression of E-cadherin and increased expression of vimentin and Snail were observed in A549 cells cocultured with MSCs. Conversely, MSC coculture-mediated autophagy positively promoted tumour EMT. Autophagy inhibition suppressed MSC coculture-mediated EMT and reduced A549 cell migration and invasion slightly. Furthermore, the migratory and invasive abilities of A549 cells were additional increased when autophagy was further enhanced by rapamycin treatment. Taken together, this work suggests that microenvironments containing MSCs can promote autophagy activation for enhancing EMT; MSCs also increase the migratory and invasive abilities of A549 lung adenocarcinoma cells. Mesenchymal stem cell-containing microenvironments and MSC-induced autophagy signalling may be potential targets for blocking lung cancer cell migration and invasion.
Background Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model. Methods Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome data in HCC Cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in Cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic features. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic properties on stemness features of HCC cells via interacting with co-cultured non-tumor cells. Results High levels of glycolysis-related metabolites and genes were present in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes’ expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival. Conclusions In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.
Background: Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model. Methods: Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome in HCC cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic feature. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic property on stemness features of HCC cells via interacting with co-cultured non-tumor cells. Results: High levels of glycolysis-related metabolites and genes presented in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes’ expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival. Conclusions: In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.
Background: Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model.Methods: Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome data in HCC Cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in Cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic features. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic properties on stemness features of HCC cells via interacting with co-cultured non-tumor cells.Results: High levels of glycolysis-related metabolites and genes were present in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes’ expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival.Conclusions: In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.