Cancer Stem Cells In Lung Cancer Research Articles

Activation of MYO1G by lncRNA MNX1-AS1 Drives the Progression in Lung Cancer.

Lung cancer represents the most prevalent cancer worldwide and causes the death of many patients. Cancer stem cells (CSCs), a subpopulation of cancer cells, have the capacities of self-renewal, unlimited proliferation, and multiple differentiation potential. The purpose of this study was to explore the potential role of long noncoding RNA (lncRNA) MNX1-AS1 on maintaining the stemness of CSC in lung cancer. CSCs were firstly sorted by flow cytometry. After the determination of the target of the present study using Gene Expression Omnibus dataset, MNX1-AS1was found to be highly expressed in lung cancer tissues and cells. Deletion of MNX1-AS1 inhibited proliferation, migration, invasion and sphere-forming abilities of CSC. Furthermore, subcellular fractionation, fluorescence in situ hybridization, RNA immunoprecipitation, and dual-luciferase experiments demonstrated that MNX1-AS1 recruited the transcription factor POU domain class 2 transcription factor 2 (POU2F2) to the nucleus and activated the myosin IG (MYO1G) expression. MYO1G overexpression partially reversed the si-MNX1-AS1-decreased stemness of CSCs. Finally, MNX1-AS1 suppression significantly repressed the growth of xenografts in vivo. Our study highlights the importance of the MNX1-AS1/POU2F2/MYO1G axis in stem cell-like properties of lung cancer cells.

EGFR-TKI resistance and MAP17 are associated with cancer stem cell like properties.

Patients with non-small-cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations generally react well to tyrosine kinase inhibitors (TKIs). However acquired resistance eventually occurs. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification and PIK3CA mutation. In recent years, cancer stem cells (CSCs) have been suggested to be involved in TKI resistance. MAP17 is aberrantly overexpressed in a number of malignancies. However, the expression pattern and function of MAP17 in CSCs are still unclear. The aim the present study was to illustrate the effect of CSC-like cells on the resistance to TKIs in EGFR mutant NSCLC cells and explore the possible role of MAP17 in CSCs. The EGFR mutant cell line PC9 was cultured under serum-deprived undifferentiated conditions. The CSC properties including expression of stem cell markers CD133, CD44, Oct-4 and ABCG2, ability of self-renewal, invasion, proliferation and tumorigenesis were examined. The expression of MAP17 was compared in sphere and parent cells. Sphere cells displayed stem cells phenotypes and were resistant to erlotinib. Sphere cells expressed higher levels of MAP17, and MAP17 was associated with self-renewal and TKI resistance. The function of MAP17 demonstrated to be partially dependent on Na-dependent glucose transporter 1. Collectively these findings suggest that MAP17 serves a role in TKI resistance through regulation of CSCs in lung cancer.

Lung cancer stem cells – the role in pathogenesis and progressive growth of cancer

Lung cancer is the main cause of cancer death worldwide. Rapid accurate diagnosis, recognition of risk factors and improvement of treatment efficacy represent the main challenges. An advanced stage of the disease at the time of diagnosis, observed in the majority of cases, makes the introduction of radical treatment impossible or ineffective. Immunotherapy was a breakthrough in achieving long-term survival in recent years. The reason for developing this type of treatment is to know the interaction between the host cells and tumor cells. Cancer stem cells theory is increasingly gaining greater significance in the world. The biological heterogeneity of lung cancer may be due to the presence of a small percentage of cancer stem cells (CSCs). CSCs are the results of genetic and epigenetic changes in normal stem cells, progenitor cells or differentiated cells. CSCs are functionally defined by their unlimited self-renewal capacity, multiple differentiation and their ability to imitate tumors. It is believed that CSCs determine unrestricted growth of tumors and their different morphology. Their ability to self-renew can be the cause of relapses even after long periods of remission. CSCs reside in niches, where they receive signals for differentiation and proliferation process. The identification of CSCs is based on the presence of specific molecules (CD133, CD44, CD90, ALDH, EpCAM). An important feature of CSCs is their resistance to conventional cancer treatment: radio therapy and chemotherapy. Presumably, CSCs are responsible for the synthesis of immunosuppressive particles, and recruiting other molecules, which have immunosuppressive properties. The paper presents the current state of knowledge on CSCs in lung cancer detailing adenocarcinoma.

The combination therapy of salinomycin and gefitinib using poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles for targeting both lung cancer stem cells and cancer cells.

PurposeLung cancer (LC) is the leading cause of cancer death worldwide. Evidences suggest that both LC cancer stem cells (CSCs) and cancer cells are supposed to be eliminated to achieve superior treatment effect against LC. Salinomycin could eradiate CSCs in various types of cancers, and gefitinib is a first-line therapy in LC. The purpose of the present study was to develop salinomycin-loaded nanoparticles (salinomycin-NPs) combined with gefitinib-loaded nanoparticles (gefitinib-NPs) to eradicate both LC CSCs and cancer cells.MethodsSalinomycin and gefitinib were encapsulated separately by poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles by the emulsion/solvent evaporation approach. The anti-LC activity of salinomycin-NPs and gefitinib-NPs was investigated.ResultsSalinomycin-NPs and gefitinib-NPs are of ~140 nm in size, high drug encapsulation efficacy and sustained release of drugs. CD133+ LC CSCs showed the characteristics of CSCs, including significantly enhanced stem cell gene expression, tumorsphere formation ability, and tumorigenicity in mice. Both salinomycin and salinomycin-NPs are capable of selectively inhibiting LC CSCs, as reflected by their enhanced cytotoxic effects toward CD133+ LC CSCs and ability to reduce tumorsphere formation in LC cell lines, whereas gefitinib and gefitinib-NPs could significantly inhibit LC cells. Salinomycin-NPs and salinomycin could reduce the population of LC CSCs in the tumors in vivo. It is noteworthy that salinomycin-NPs combined with gefitinib-NPs inhibited the growth of tumors more efficiently compared with salinomycin combined with gefitinib or single salinomycin-NPs or gefitinib-NPs.ConclusionSalinomycin-NPs combined with gefitinib-NPs represent a potential approach for LC by inhibiting both LC CSCs and cancer cells.

Engineering cancer stem-like cells from normal human lung epithelial cells.

It has been proposed that a subpopulation of tumour cells with stem cell-like characteristics, known as cancer stem cells (CSCs), drives tumour initiation and generates tumour heterogeneity, thus leading to cancer metastasis, recurrence, and drug resistance. Although there has been substantial progress in CSC research into many solid tumour types, an understanding of the biology of CSCs in lung cancer remains elusive, mainly because of their heterogeneous origins and high plasticity. Here, we demonstrate that engineered lung cancer cells derived from normal human airway basal epithelial cells possessed CSC-like characteristics in terms of multilineage differentiation potential and strong tumour-initiating ability. Moreover, we established an in vitro 3D culture system that allowed the in vivo differentiation process of the CSC-like cells to be recapitulated. This engineered CSC model provides valuable opportunities for studying the biology of CSCs and for exploring and evaluating novel therapeutic approaches and targets in lung CSCs.