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Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.
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Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.
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Humans , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , B7-H1 Antigen/metabolism , Ligands , Liver Neoplasms/pathology , RNA, Small Interfering/metabolism , Neoplastic Stem Cells/physiology , Cell Line, Tumor , Cell ProliferationABSTRACT
【Objective】 To investigate the role of microRNA-218 (miR-218) in regulating prostate cancer (PCa) cell stemness and epithelial-mesenchymal transition (EMT). 【Methods】 PCa cell line stably overexpressing miR-218 was constructed with lentivirus transfection. The expression of miR-218 was detected with real-time fluorescence quantitative polymerase chain reaction (q-PCR). The migration ability was detected with Transwell assay. The expression of EMT related proteins were detected with Western blot. The properties of cells were determined with colony formation and tumor sphere formation assays. 【Results】 The results of q-PCR showed that the mRNA level of miR-218 was significantly lower in PCa cell lines LNCaP and C4-2 than in BPH-1. Transwell assay showed that miR-218 inhibited the migration of PCa cells. Western blot showed that the expression of EMT related proteins were inhibited by miR-218. Colony formation and tumor sphere formation assays showed that overexpression of miR-218 significantly inhibited the properties of cells. 【Conclusion】 The expression of miR-218 is downregulated in PCa cell lines. miR-28 can inhibit cell migration, EMT and cancer stem cell properties.
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Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.
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OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
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Female , Humans , Cell Line, Tumor , HeLa Cells , Neoplastic Stem Cells/metabolism , RNA, Small Interfering/metabolism , Uterine Cervical Neoplasms/metabolismABSTRACT
BACKGROUND: Bladder cancer stem cells could promote the recurrence and drug resistance of bladder cancer. Numerous studies have shown that keratin 6B (KRT6B) is involved in the production and progression of tumors, and is closely related to the prognosis of tumors. OBJECTIVE: To observe the expression of keratin 6B in CD44+ bladder cancer stem cells and to show the influence of keratin 6B on proliferation, migration, and self-renewal of bladder cancer stem cells, and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients. METHODS: (1) CD44+ 5637 bladder cancer stem cells were isolated by magnetic active cell sorting. Cancer stem cell-related gene expression of SOX2, OCT4, and NANOG was detected via real-time polymerase chain reaction. The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44+ cells. Keratin 6B expression was detected in CD44+ bladder cancer stem cells by real-time polymerase chain reaction. (2) The CD44+5637 bladder cancer stem cells were divided into two groups. In the keratin 6B siRNA group, keratin 6B small interfering RNA was transfected into CD44+ bladder cancer stem cells. Untransfected CD44+ bladder cancer stem cells were used as the black control group. Cells were collected at 2 days post-transfection. The proliferation, migration, and self-renewal capacity of keratin 6B siRNA CD44+ bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively. (3) Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B. (4) ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer. RESULTS AND CONCLUSION: (1) Cancer stem cell-related genes (SOX2, OCT4, NANOG) and keratin 6B expression was higher in CD44+ cells isolated by magnetic active cell sorting compared with CD44- cells (P < 0.05). Cell proliferation, migration, and in vitro spheroid formation were significantly increased (P < 0.05). Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44+ bladder cancer stem cells (P < 0.05). (2) Compared with the blank control group, the proliferation and migration of CD44+ bladder cancer stem cells after transfection of keratin 6B small interfering RNA (P < 0.05), and the number of tumorsphere significantly diminished (P < 0.05); the expression of Notch1 and Hes1 mRNA increased (P < 0.05). (3) Keratin 6B and CD44v6 were significantly different in bladder cancer tissue (P=0.006). The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B. (4) The results showed that keratin 6B was highly expressed in CD44+ bladder cancer stem cells, and could promote the proliferation, migration, and self-renewal capacity of bladder cancer stem cells. The high expression of keratin 6B contributes to improving the survival of bladder cancer patients.
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Thyroid cancer is highly heterogeneous and has three main types of histopathology: low-malignant papillary thyroid cancer, follicular cancer, and high-malignant undifferentiated cancer. It has recently been hypothesized that thyroid cancer stem cell (TCSC) plays a major role in both cancer initiation and metastasis, but the origin of TCSC and underlying mechanism in the development of thyroid cancer are still unclear. In this article, we introduced the origin theory of thyroid cancer from TCSC and the relation of TCSC to immune system and tumor microenvironment as well as TCSC-based treatment strategy. This will provide a new direction for the treatment of thyroid cancer, so as to improve the prognosis of patients with refractory thyroid cancer.
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Objective: To investigate the potential effect of Lysimachia capillipes capilliposide (LCC) on the chemo sensitivity and the stemness of human ovarian cancer cells. Methods: Cell Counting Kit-8 (CCK8) was used to measure the IC
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Objective To explore the effect of epigenetic regulator polycomb group factor I ( PCGFI) on the enrichment of colorectal cancer stem cells and its mechanism. Methods Meta-analysis was used to predict the expression of PCGFI in normal and colorectal cancer tissues. The gene expression of PCGFI in colorectal cancer tumor cells and normal intestinal epithelium cells was detected by Real-time PCR. PCGFI loss-of-function subclone was generated in HCT116, and sternness was evaluated by spheroid formation. The effects of PCGFI on sternness markers and the key proteins in Wnt and Notch pathways were detected by Oncomine and GEPIA database, Real-time PCR and Western blotting. Results PCGFI was markedly upregulated in colorectal cancer cells and tissues. PCGFI knockdown strongly inhibited tumor sphere formation of HCT116 and sternness markers expression. There was a positive correlation between PCGFI and the key proteins in Wnt and Notch pathways. PCGFI knockdown reduced the expression of (3-catenin in Wnt signaling pathway. Conclusion PCGFI affects the enrichment of colorectal cancer stem cells and regulates the expression of key proteins in the signal pathway which is related to colorectal cancer stem cells self-renewal.
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The bone marrow microenvironment, also known as the bone marrow niche, plays a critical role in maintaining the functions of hematopoietic stem cells. Under physiological conditions, various bone marrow cells regulate each other to sustain hematopoietic homeostasis. However, bone marrow cells gain abnormal function under pathological conditions to cause and promote the occurrence of leukemia and induce drug resistance. Recent findings indicate that abnormal proliferation and differentiation are not the sole reason to cause leukemia. Different types of bone marrow cells also induce intercellular adhesion, abnormally secrete cytokines and chemokines, accelerating leukemia's progress. This article reviews the multiple signaling pathways that regulate the formation and progress of leukemia bone marrow niche, such as C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 signaling pathway, et al. It emphasizes that targeting leukemia bone marrow niche is a vital strategy for improving the leukemia treatment.
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Colorectal cancer stem cells are undifferentiated tumorigenic cells with malignant phenotypic characteristics in colorectal cancer and considered as the main cause of tumor recurrence, drug resistance, and metastasis through self-renewal and differentiated cloning. Colorectal cancer stem cells and various components in the tumor microenvironment are interdependent and influence one another. The relationship between tumor stem cells and other components in the tumor microenvironment may play an important role in the treatment of colorectal cancer. This review summarizes this relationship.
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Inhibitor of DNA binding 1 (ID1) has an aberrantly high expression in multiple cancer tissues, including colon cancer, lung cancer, breast cancer, and so on, which is closely related to cancer aggressiveness and poor clinical outcomes in cancer patients. It has been reported that ID1 maintains colorectal cancer cells (CRCs) stemness traits and contributes to the CRC drug resistance. While, the biological molecular mechanisms have not been fully elucidated. In this research, we found that ID1 upregulates octamer binding transcription factor (OCT4) protein level as well as OCT4 signaling pathway via Western blot, gene set enrichment analysis (GSEA), dual-luciferase reporter assay, and real-time PCR. Through the in vitro sphere formation assay, we found that overexpression of OCT4 reverses the inhibitory effect of knocking down ID1 on CRC sphere formation ability. With the help of JASPAR and GEPIA database, we predicted a novel transcriptional repressor—forkhead box D3 (FOXD3) of OCT4. Finally, by using co-immunoprecipitation (Co-IP), confocal and real-time PCR, we demonstrated that ID1 interacts with FOXD3 to inhibit its transcriptional repression activity and therefore to upregulate OCT4 transcription and OCT4 signaling pathway. In conclusion, this study provides a new theoretical basis for the regulation mechanism of colon cancer stem cells, and the newly found protein-protein interaction of ID1-FOXD3 provides a potential drug target for the therapy of CRC.
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Cancer stem cells (CSCs) with their self-renewal ability are accepted as cells which initiate tumors. CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies, including radiotherapy and chemotherapy. Chimeric antigen receptor (CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens (TAAs) by which they accurately target and kill cancer cells. In recent years, CAR-T cell therapy has shown more efficiency in cancer treatment, particularly regarding blood cancers. The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy. Here we review the CSC markers that have been previously targeted with CAR-T cells, as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future. Furthermore, we will detail the most important obstacles against CAR-T cell therapy and suggest solutions.
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Actin-like 6A (ACTL6A), also known as BAF53A, is an SWI / SNF subunit of chromatin-remodeling factors and plays an important role in regulating stem cell function. Recent studies found that ACTL6A was involved in tumor occurrence and development. However, the mechanism of ACTL6A in cisplatin resistance is still unclear. This study investigated the biological function and molecular mechanism of ACTL6A in maintaining cancer stem cell function and cisplatin resistance. First, analysis from TCGA, GEO, and GEPIA databases showed that ACTL6A expression levels in lung adenocarcinoma (LUAD) tissues and cisplatin resistant cells were dramatically higher than that in adjacent normal tissues and cisplatin sensitive cells (P < 0. 05), and ACTL6A high expression was positively associated with a poor prognosis of LUAD. Knockdown of ACTL6A enhanced cisplatin sensitivity (P < 0. 05), reduced tumor sphere (P<0. 05), inhibited cell migration (P<0. 05), and promoted cell apoptosis (P<0. 05) in A549 cells. Western blotting showed that knockdown of ACTL6A increased the protein expression of E-cadherin, and decreased the protein expression of N-cadherin, vimentin, and twist. Moreover, knockdown of ACTL6A inhibited the expression of cancer stem cell markers, including ALDH3A1, ALDH4A1, SOX2, OCT4, and Nanog. Subsequently, Hippo / YAP signaling-related proteins were analyzed by Western blotting. The results showed the expression of beta-TRCP and YAP was decreased in A549 cell with knockdown of ACTL6A. However, phosphorylation levels at S127 and S397 of YAP were increased and inhibited translocation of YAP into the nucleus for regulating related gene expression. In summary, ACTL6A maintained the stemness of lung cancer stem cells and promoted cisplatin resistance in A549 cells by inhibiting activation of the Hippo signaling pathway.
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Objective To study the stemness characteristics of uterine corpus endometrial carcinoma(UCEC)and its potential regulatory mechanism.Methods Transcriptome sequencing data of UCEC was obtained from The Cancer Genome Atlas.Gene expression profile was normalized by edgeR package in R3.5.1.A one-class logistic regression machine learning algorithm was employed to calculated the mRNA stemness index(mRNAsi)of each UCEC sample.Then,the prognostic significance of mRNAsi and candidate genes was evaluated by survminer and survival packages.The high-frequency sub-pathways mining approach(HiFreSP)was used to identify the prognosis-related sub-pathways enriched with differentially expressed genes(DEGs).Subsequently,a gene co-expression network was constructed using WGCNA package,and the key gene modules were analyzed.The clusterProfiler package was adopted to the function annotation of the modules highly correlated with mRNAsi.Finally,the Human Protein Atlas(HPA)was retrieved for immunohistochemical validation.Results The mRNAsi of UCEC samples was significantly higher than that of normal tissues(
Subject(s)
Female , Humans , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Endometrial Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Mad2 Proteins , Multigene Family , Neoplastic Stem Cells , Prognosis , SecurinABSTRACT
@#[Abstract] Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation, migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX(35 µg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.
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Background: The promising improvement in the clinical outcome of lung cancer can be possibly achieved by identification of the molecular events that underlie its pathogenesis. Cancer stem cell (CSC) being one of the subsets of tumor majorly participates in drug resistance and treatment failure because of the moderate cell cycle, lower proliferation, and increased expression of DNA repair and anti-apoptosis genes. Although many putative CSC markers exist, a precise characterization for non-small cell lung cancer is of utmost importance due to increased mortality rate and lack of targeted therapies. Hence, the article focuses on the expression of stemness-associated markers, namely octamer-binding transcription factor 4 (OCT4), NANOG, and sex-determining region Y-box 2 (SOX2) in non-small cell lung cancer (NSCLC) patients. Methods: The expression of OCT4, NANOG, and SOX2 were evaluated in 32 histopathologically confirmed NSCLC tissues using real-time polymerase chain reaction. The obtained expression was correlated with clinical and pathological manifestations using the statistical test such as Student's t-test and Pearson correlation in varied statistical software. Results: Results showed a significantly higher expression of OCT4 and NANOG compared to SOX2 in the tumor tissues. When the expression of these markers was correlated with the clinical parameters, higher expression was seen in males, patients with age above 60 years, and in adenocarcinoma subtype. In correlation with the habit, higher expression of OCT4 and SOX2 was observed in habituated patients. Expression of NANOG and OCT4 was higher even in patients with poor differentiation. Conclusion: The expression and prognostic significance of CSC markers obviously vary depending on histological NSCLC subtype. Importantly, our findings suggest that OCT4, SOX2, and NANOG network together may be promising for ongoing targeted therapies in specific NSCLC subgroups
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Objective: To give a retrospective bibliometric analysis of documents about the breast cancer stem cell (BCSC) and reveal the hotspots and trends of global output. Methods: Articles about the research of BCSC between 2014 and 2019 were retrieved in PubMed and Scopus databases, and SciVal was used to evaluate the global scholarly output and identify the most active factors, such as publications, countries, institutions, and top journal percentile, from the indicators of Field-Weighted Citation Impact (FWCI), CiteScore (CS), keywords and topic prominence percentile. Research hotspots and trends were discussed in detail. Results: A total of 4 700 publications on the research of BCSC from 2014 to 2019 were retrieved in this study with FWCI 1.73. The USA was the top country with a total of 1 742 publications and National Institutes of Health was the top institution both in total citation and FWCI. Non-coding RNA (ncRNA), mesenchymal stem cells, and immunotherapy were the most frequently used topics in BCSC. Conclusion: Researches on the correlation of BCSC and ncRNA, tumor microenvironment, and immunotherapy are the hotspots and trends in BCSC.
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Objective: To study the role of pancreatic cancer stem cells in radiotherapy resistance of pancreatic cancer. Methods: CD133+ pancreatic cancer stem cells were obtained by using magnetic cell sorting. MTT and flow cytometry were used to observe the proliferation activity and apoptosis of different cell subsets of pancreatic cancer after radiation treatment. Then flow cytometry, Western blot and qRT-PCR were used to observe the expression changes of CD133 in pancreatic cancer cells after radiation treatment. Finally, the cell cycle distribution of different subgroup cells was observed by flow cytometry. Results: Compared with unselected cells and CD133- cells, CD133+ stem cells had the highest survival rate and the lowest apoptosis rate after radiation treatment. The proportion of CD133+ stem cells increased and the expressions of CD133 protein and RNA increased in pancreatic cancer cells. CD133+ stem cells had the highest ratio of G0/G1 phase compared with unsorted cells and CD133- cells, and the difference was statistically significant. Conclusion: CD133+ pancreatic cancer stem cells are one of the important causes of radiotherapy resistance in pancreatic cancer cells, and the increased proportion of G0/G1 phase may be one of the mechanisms.
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@#[Abstract] Objective: To investigate the effect of 18H12, a functional monoclonal antibody that can target gastric cancer stem cells, on the self-renewal and invasion ability of gastric cancer cells. Methods: The gastric cancer cell line PAMC-82 was used as cell model, the expression of ENO1 (enolase-1) on the membrane surface of its parental cells and enriched stem cells by sphere culture was detected by Flow cytometry. Flow cytometry was used to separate ENO1+ cells and ENO1- cells to detect their self-renewal ability and invasion ability. With the commercial ENO1 antigen and antibody as the samples, CoIP (co-immunoprecipitation) was used to verify whether 18H12 antibody targeting ENO1 could able to accurately recognize ENO1. After being treated with 18H12 for 12 h, 24 h and 48 h, the selfrenewal and invasion ability of PAMC-82 cells were detected by methylcellulose pelletization experiment and Transwell chamber assay, respectively. Results: Flow cytometry showed that the expression of ENO1 on the membrane surface of PAMC-82 sphere cells was significantly higher than that of its parental cells (P<0.01), so ENO1 could be a potential target for targeting gastric cancer stem cells. The self-renewal ability and invasion ability of the sorted ENO1+ cells were significantly stronger than those of the ENO1- cells and the parental cells (P<0.05 or P<0.01). 18H12 antibody could accurately recognize ENO1, which was consistent with the commercial antibody recognition band. 18H12 could significantly inhibit self-renewal ability and invasion ability of PAMC-82 cells (P<0.01). Conclusion: Monoclonal antibody 18H12 can significantly inhibit the self-renewal and invasion of gastric cancer stem cells and is expected to be a candidate antibody drug targeting gastric cancer stem cells.