scholarly journals CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bing-zhou Xue ◽  
Wei Xiang ◽  
Qing Zhang ◽  
Hao-fei Wang ◽  
Yu-jie Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Glioma Cells ◽  
Conditioned Media ◽  
Cell Counting ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation ◽  
Stromal Stem Cells

Abstract Background The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. Methods Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. Results Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. Conclusions CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.

scholarly journals Casticin inhibits epithelial-mesenchymal transition of liver cancer stem cells of the SMMC-7721 cell line through downregulating Twist

2014 ◽  
Vol 7 (5) ◽  
pp. 1625-1631 ◽  
Author(s):  
MENG HE ◽  
XIAO-CHENG CAO ◽  
GUI-CHENG HE ◽  
XI-FENG SHENG ◽  
XIAO-HONG AI ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Liver Cancer Stem Cells

scholarly journals Bioinformatics analysis and biological experiments support an emerging role of ELK3 in glioma

2021 ◽  
Author(s):  
Jiangtao Dong ◽  
Hui Xu ◽  
Fulei Chen ◽  
Shilong Wang ◽  
Yang Wang ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Biological Properties ◽  
Cell Counting ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
Interactive Analysis ◽  
Prognostic Prediction

IntroductionGlioma is a malignant tumor that recurs easily. This study aimed at investigating the biological effect of ELK3 in epithelial-mesenchymal transition (EMT) and its prognostic value.Material and methodsBioinformatics analyses were performed to determine the expression and prognostic value of ELK3. The biological properties of glioma cells (A172 and LN229) were evaluated by cell counting kit-8, plate cloning and transwell assays. Gene Expression Profiling Interactive Analysis (GEPIA) website was used to analyze the relationship between ELK3 expression and EMT-related markers. Western blotting was applied to detect the protein levels.ResultsELK3 is highly expressed in glioma and significantly associated with poor prognosis (p < 0.05), presenting promising value in the diagnosis and prognostic prediction of glioma. Further biological assays revealed that cell viability was notably reduced after down-regulating ELK3 (p < 0.01). The numbers of colonies formed by A172 (145.30 ± 12.86 vs. 300.30 ± 11.68) and LN229 (125.70 ± 4.04 vs. 256.00 ± 20.07) cells were decreased after transfection of si-ELK3 (p < 0.01). The numbers of invaded and migrated glioma cells in si-ELK3 group were decreased by about half (p < 0.01). Moreover, ELK3 was positively correlated with N-Cadherin (R = 0.21), Snail1 (R = 0.43), Slug (R = 0.6) and Vimentin (R = 0.35), and depletion of ELK3 reduced the levels of these EMT-related markers more than a half (p < 0.01).ConclusionsOur observations illustrated that ELK3 was highly expressed in glioma and played a promoting role in the growth and mobility of glioma cells partly by modulating EMT progress.

scholarly journals E-CADHERIN EXPRESSION DOWNREGULATION ELEVATES TUMOROGENIC POTENTIAL OF HUMAN COLON CANCER CELL LINE HCT116 VIA INCREASE IN CANCER STEM CELLS AMOUNT

2016 ◽  
Vol 15 (3) ◽  
pp. 6-14 ◽  
Author(s):  
M. D. Farmakovskaya ◽  
N. V. Khromova ◽  
B. P. Kopnin ◽  
P. B. Kopnin
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Human Colon ◽  
Colon Cancer Cell Line ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
E Cadherin

Introduction. E-cadherin aberrant expression or complete loss is common for a number of human malignant neoplasms, and can be a launching mechanism of an epithelial-mesenchymal transition. Passing through epithelial-mesenchymal transition could in turn promote to the acquisition of so called cancer stem cell phenotype by the transformed cells. The objective of the present study is to reveal the influence of E-cadherin expression level on the amount of cancer stem cells in human colon cancer cell line HCT116. Materials and methods. We have created cell sublines with E-cadherin up- and downregulation and assessed the percentage of cancer stem cells using tumor formation assay, clonogenic assay; we also evaluated profile of cell pluripotency markers. Results and conclusion. We have shown that the proportion of cancer stem cells in human colon adenocarcinoma cell line HCT116 depends on the E-cadherin expression level. E-cadherin expression downregulation results in elevated expression of pluripotency genes and in the increase of proportion of cancer stem cells via activation of Wnt/ß-signalling pathway. E-cadherin upregulation has a reverse effect and decreases the amount of HCT116 cancer stem cells. Thus, E-cadherin expression restoration seems prospective in colorectal anticancer therapy.

scholarly journals MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Development ◽  
Special Focus ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Different Cell Types

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

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