Targeting of CD133+ Cancer Stem Cells by Mesenchymal Stem Cell Expressing TRAIL Reveals a Prospective Role of Apoptotic Gene Regulation in Non-Small Cell Lung Cancer

Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.

Download Full-text

LIFE SPAN PREDICTION AT METASTATIC NON-SMALL CELL LUNG CANCER

Problems in oncology ◽

10.37469/0507-3758-2018-64-4-522-527 ◽

2018 ◽

Vol 64 (4) ◽

pp. 522-527

Author(s):

Aleksey Shutko ◽

Viktor Mus

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Small Cell Lung Cancer ◽

Life Span ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Hemopoietic Stem Cells ◽

Small Cell Lung ◽

Individual Life

Individual parameters of circulating hemopoietic stem cells (HSC) lymphoid origin were measured by cytofluorometry before treatment of patients with metastatic non-small cell lung cancer and were retrospectively compared with individual life span's (LS). The possibility of poor prognosis of treatment's results (LS

Download Full-text

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721130700 ◽

2020 ◽

Vol 20 (17) ◽

pp. 2074-2081

Author(s):

Onur Tokgun ◽

Pervin E. Tokgun ◽

Kubilay Inci ◽

Hakan Akca

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Strategy ◽

Small Cell ◽

Small Cell Lung ◽

Expression Levels ◽

Qrt Pcr ◽

Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

Download Full-text

Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

Molecules ◽

10.3390/molecules26041056 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1056 ◽

Cited By ~ 1

Author(s):

Nazilah Abdul Satar ◽

Mohd Nazri Ismail ◽

Badrul Hisham Yahaya

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cellular Proliferation ◽

Combined Treatment ◽

Small Cell ◽

Cytotoxic Agents ◽

Small Cell Lung ◽

Proliferation Activity

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.

Download Full-text

Long noncoding RNA MCF2L‐AS1 promotes the cancer stem cell‐like traits in non‐small cell lung cancer cells through regulating miR ‐873‐5p level

Environmental Toxicology ◽

10.1002/tox.23142 ◽

2021 ◽

Author(s):

Shouguo Li ◽

Liancheng Lin

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Small Cell ◽

Small Cell Lung

Download Full-text

p53-regulated GML gene expression in non-small cell lung cancer: Relation to cisplatin chemosensitivity

Lung Cancer ◽

10.1016/s0169-5002(00)80654-6 ◽

2000 ◽

Vol 29 (1) ◽

pp. 193

Author(s):

M Higashiyama ◽

K Kodama ◽

H Yokouchi ◽

K Takami ◽

Y Miyoshi ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

Download Full-text

Effects of fine air particulates on gene expression in non-small-cell lung cancer

Advances in Medical Sciences ◽

10.1016/j.advms.2016.12.003 ◽

2017 ◽

Vol 62 (2) ◽

pp. 295-301 ◽

Cited By ~ 5

Author(s):

Biao Yang ◽

Xinming Li ◽

Dongmei Chen ◽

Chunling Xiao

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

Download Full-text

Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer

Communications Biology ◽

10.1038/s42003-021-01842-7 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Ling Cai ◽

Hongyu Liu ◽

Fang Huang ◽

Junya Fujimoto ◽

Luc Girard ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Neuroendocrine Cells ◽

Immune Gene ◽

Small Cell Lung ◽

Immune Gene Expression ◽

Pulmonary Neuroendocrine Cells

AbstractSmall cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.

Download Full-text

520 Validation of Nanostring for FGFR1 gene expression analysis in squamous non-small cell lung cancer (sqNSCLC) tissue

European Journal of Cancer ◽

10.1016/s0959-8049(14)70646-x ◽

2014 ◽

Vol 50 ◽

pp. 169

Author(s):

C. Rooney ◽

C. Geh ◽

V. Williams ◽

C. Cresswell ◽

K. Al-Kadhimi ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Expression Analysis ◽

Cell Lung Cancer ◽

Gene Expression Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Fgfr1 Gene

Download Full-text

Predicting Diagnostic Gene Biomarkers for Non-Small-Cell Lung Cancer

BioMed Research International ◽

10.1155/2016/3952494 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8

Author(s):

Bin Liang ◽

Yang Shao ◽

Fei Long ◽

Shu-Juan Jiang

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Association Network ◽

Small Cell Lung ◽

Functional Association ◽

Functional Association Network ◽

Gene Modules

Lung cancer is the primary reason for death due to cancer worldwide, and non-small-cell lung cancer (NSCLC) is the most common subtype of lung cancer. Most patients die from complications of NSCLC due to poor diagnosis. In this paper, we aimed to predict gene biomarkers that may be of use for diagnosis of NSCLC by integrating differential gene expression analysis with functional association network analysis. We first constructed an NSCLC-specific functional association network by combining gene expression correlation with functional association. Then, we applied a network partition algorithm to divide the network into gene modules and identify the most NSCLC-specific gene modules based on their differential expression pattern in between normal and NSCLC samples. Finally, from these modules, we identified genes that exhibited the most impact on the expression of their functionally associated genes in between normal and NSCLC samples and predicted them as NSCLC biomarkers. Literature review of the top predicted gene biomarkers suggested that most of them were already considered critical for development of NSCLC.

Download Full-text