scholarly journals BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chi-Ming Lee ◽  
Yen-Hao Su ◽  
Thanh-Tuan Huynh ◽  
Wei-Hwa Lee ◽  
Jeng-Fong Chiou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Tumor Cell Death ◽  
Invasion And Migration ◽  
Tumor Sphere ◽  
Flow Cytometric Method ◽  
Number Of Factors ◽  
Radiation Induced ◽  
And Migration ◽  
Sphere Formation

For many malignancies, radiation therapy remains the second option only to surgery in terms of its curative potential. However, radiation-induced tumor cell death is limited by a number of factors, including the adverse response of the tumor microenvironment to the treatment and either intrinsic or acquired mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs). In this study, we demonstrated that using different doses of irradiation led to the enrichment of CD133+Mahlavu cells using flow cytometric method. Subsequently, CD133+Mahlavu cells enriched by irradiation were characterized for their stemness gene expression, self-renewal, migration/invasion abilities, and radiation resistance. Having established irradiation-enriched CD133+Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene (PT), found abundantly in blueberries, against irradiation-enriched CSCs. It was shown that PT treatment dose-dependently reduced the enrichment of CD133+Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere formation, reduced stemness gene expression, and suppressed invasion and migration abilities as well as increasing apoptosis of CD133+Mahlavu CSCs. Based on our experimental data, pterostilbene could be used to prevent the enrichment of CD133+hepatoma CSCs and should be considered for future clinical testing as a combined agent for HCC patients.

Role of syndecan-1 and exogenous heparin in hepatoma sphere formation

2020 ◽  
Vol 98 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Shih-Chiang Lin ◽  
Ching-Po Wu ◽  
TingTing Tseng ◽  
Yaoyun Jhang ◽  
Shao-Chen Lee
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cd44 Expression ◽  
Tumor Sphere ◽  
Family Protein ◽  
Sphere Formation ◽  
Development Application

Glycosaminoglycan-modified proteoglycans play important roles in many cell activities, including cell differentiation and stem cell development. Tumor sphere formation ability is one of properties in cancer stem cells (CSCs). The correlation between CSC markers and proteoglycan remains to be clarified. Upon hepatoma sphere formation, expression of CSC markers CD13, CD90, CD133, and CD44, as well the syndecan family protein syndecan-1 (SDC1), increased as analyzed by PCR. Further examination by suppression of CD13 expression showed downregulation of SDC1 and CD44 gene expression, whereas suppression of SDC1 gene expression downregulated CD13 and CD44 gene expression. Suppression of SDC1 gene expression also suppressed sphere development, as analyzed by a novel sphereocrit assay to quantify the level of sphere formation. The heparin disaccharide components, but not those of chondroitin disaccharide, changed with hepatoma sphere development, revealing the increased levels of N-sulfation and 2-O-sulfation. These explained the inhibition of hepatoma sphere formation by exogenous heparin. In conclusion, we found that SDC1 affected CSC marker CD13 and CD44 expression. SDC1 proteoglycan and heparin components changed and affected hepatoma sphere development. Application of heparin mimics in reduction of hepatoma stem cells might be possible.

scholarly journals BCOR Internal Tandem Duplication Expression in Neural Stem Cells Promotes Growth, Invasion, and Expression of PRC2 Targets

2021 ◽  
Vol 22 (8) ◽  
pp. 3913
Author(s):  
Satoshi Nakata ◽  
Ming Yuan ◽  
Jeffrey A. Rubens ◽  
Ulf D. Kahlert ◽  
Jarek Maciaczyk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Tandem Duplication ◽  
Target Genes ◽  
Cellular Growth ◽  
Central Nervous System Tumor ◽  
Internal Tandem Duplication ◽  
Invasion And Migration ◽  
Human Neural Stem Cells ◽  
And Migration

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.

scholarly journals CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongliang Liu ◽  
Guiqin Wang ◽  
Jiasi Zhang ◽  
Xue Chen ◽  
Huailong Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Stem Cell Marker ◽  
Hematopoietic Stem ◽  
Chemotherapy Drugs ◽  
And Migration ◽  
Acute Myeloid

Abstract Background Leukemia stem cells (LSCs) are responsible for the initiation, progression, and relapse of acute myeloid leukemia (AML). Therefore, a therapeutic strategy targeting LSCs is a potential approach to eradicate AML. In this study, we aimed to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs. Methods Microarray gene expression data were used to investigate candidate AML-LSC-specific markers. CD9 expression in AML cell lines, patients with AML, and normal donors was evaluated by flow cytometry (FC). The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration, and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. The effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed with regard to proliferation, drug resistance, and migration. Results CD9, a cell surface protein, was specifically expressed on AML LSCs but barely detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibit more resistance to chemotherapy drugs and higher migration potential than do CD9-negative (CD9−) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting that CD9+ cells define the LSC population. Furthermore, we identified that A2M plays a crucial role in maintaining CD9+ LSC stemness. Knockdown of A2M impairs drug resistance and migration of CD9+ cells. Conclusion Our findings suggest that CD9 is a new biomarker of AML LSCs and is a promising therapeutic target.

scholarly journals Silencing of BACH1 inhibits invasion and migration of prostate cancer cells by altering metastasis-related gene expression

2017 ◽  
Vol 46 (7) ◽  
pp. 1495-1504 ◽  
Author(s):  
Neda Shajari ◽  
Sadaf Davudian ◽  
Tohid Kazemi ◽  
Behzad Mansoori ◽  
Shima Salehi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Related Gene ◽  
Prostate Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

scholarly journals Gambogic Acid Efficiently Kills Stem-Like Colorectal Cancer Cells by Upregulating ZFP36 Expression

2018 ◽  
Vol 46 (2) ◽  
pp. 829-846 ◽  
Author(s):  
Fang Wei ◽  
Tong Zhang ◽  
Zhi Yang ◽  
Jian-Chang Wei ◽  
Hong-Fen Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Signaling Pathway ◽  
Bioluminescence Imaging ◽  
Side Population ◽  
Gambogic Acid ◽  
Tumor Sphere ◽  
Sphere Formation

Background/Aims: Gambogic acid (GA), the main active compound of Gamboge hanburyi, has been reported to be a potential novel antitumor drug. Whether GA inhibits putative cancer stem cells (CSCs), which are considered to be the major cause of cancer treatment failure, remains largely unknown. This study investigated whether GA inhibits the CSCs of colorectal cancer (CRC) and its possible mechanisms. Methods: We performed CCK8 and tumor sphere formation assays, percentage analysis of both side population and CD133+CD44+ cells, and the detection of stem cells markers, in order to assess the role of GA in inhibiting the stem celllike features of CRC. An mRNA microarray was performed to identify the downstream gene affected by GA and rescue assays were performed to further clarify whether the downstream gene is involved in the GA induced decrease of the stem cell-like CRC population. CRC cells were engineered with a CSC detector vector encoding GFP and luciferase (Luc) under the control of the Nanog promoter, which were utilized to investigate the effect of GA on putative CSC in human tumor xenograft-bearing mice using in vivo bioluminescence imaging. Results: Our results showed that GA significantly reduced tumor sphere formation and the percentages of side population and CD133+CD44+ cells, while also decreasing the expression of stemness and EMT-associated markers in CRC cells in vitro. GA killed stem-like CRC cells by upregulating the expression of ZFP36, which is dependent on the inactivation of the EGFR/ ERK signaling pathway. GFP+ cells harboring the PNanog-GFP-T2A-Luc transgene exhibited CSC characteristics. The in vivo results showed that GA significantly inhibited tumor growth in nude mice, accompanied by a remarkable reduction in the putative CSC number, based on whole-body bioluminescence imaging. Conclusion: These findings suggest that GA significantly inhibits putative CSCs of CRC both in vitro and in vivo by inhibiting the activation of the EGFR/ ERK/ZFP36 signaling pathway and may be an effective drug candidate for anticancer therapies.

Cyclosporin A promotes invasion and migration of extravillous trophoblast cells derived from human induced pluripotent stem cells and human embryonic stem cells

2020 ◽  
Author(s):  
Jiaxing Wang ◽  
Ping Long ◽  
Shengnan Tian ◽  
Weihua Zu ◽  
Jing Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Extravillous Trophoblast ◽  
Invasion And Migration ◽  
And Migration ◽  
Induced Pluripotent

Abstract Background Extravillous trophoblast (EVT) cells play an essential role in the maternal-fetal interaction. Although abnormal development and function of EVT cells, including impaired migration and invasion capability, are believed to be etiologically linked to severe pregnancy disorders including pre-eclampsia (PE), the associated molecular mechanisms are not clear ascribed to the lack of an appropriate cell model in vitro. Cyclosporine A (CsA) is a macrolide immunosuppressant and is also used in clinic to improve pregnancy outcomes. However, whether CsA has any effects on the function of EVT cells has not been well investigated. Methods In this study, we induced differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into EVT cells (hiPSC-EVT and hESC-EVT cells, respectively) by Y27632, NRG1, A83-01 and matrigel, and collected these derived EVT cells by flow cytometry for sorting cells positive for double HLA-G and KRT7, which are EVT markers. We then investigated the effects of CsA on the invasion and migration of these derived EVT cells. Results We found that the hiPSC-EVT and hESC-EVT cells expressed high levels of the EVT markers such as KRT7, ITGA5 and HLA-G but low levels of OCT4, a stem cell marker, and that CsA significantly promoted the invasion and migration of hiPSC-EVT and hESC-EVT cells. Conclusions We successfully generated hiPSC/hESC-derived human EVT cells, which may be applicable for investigating the remodeling process of spiral arteries remodeling and the possible mechanisms of EVT-related diseases in vitro. Furthermore, our findings provide direct evidence that CsA regulates the function of EVT cells and molecular basis by which CsA may be used to treat pregnancy complications in clinic associated with deficient EVT function.

scholarly journals Silencing of MBD1 and MeCP2 in prostate-cancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes

2008 ◽  
Vol 28 (6) ◽  
pp. 319-326 ◽  
Author(s):  
Ahmed Yaqinuddin ◽  
Farhat Abbas ◽  
Syed Z. Naqvi ◽  
Mohammad U. Bashir ◽  
Romena Qazi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Mrna Expression ◽  
Cellular Proliferation ◽  
Expression Profiles ◽  
Boyden Chamber ◽  
Invasion And Migration ◽  
Pc3 Cells ◽  
And Migration

Alterations in genomic CpG methylation patterns have been found to be associated with cell transformation and neoplasia. Although it is recognized that methylation of CpG residues negatively regulates gene expression, how the various MBPs (methyl-binding proteins) contribute to this process remains elusive. To determine whether the two well characterized proteins MeCP2 (methyl-CpG-binding protein 2) and MBD1 (methyl-CpG-binding domain 1) have distinct or redundant functions, we employed RNAi (RNA interference) to silence their expression in the prostate cancer-derived PC3 cell line, and subsequently compared cell growth, invasion and migration properties of these cell lines in addition to their respective mRNA-expression profiles. Cells devoid of MeCP2 proliferated more poorly compared with MBD1-deficient cells and the parental PC3 cells. Enhanced apoptosis was observed in MeCP2-deficient cells, whereas apoptosis in parental and MBD1-deficient cells appeared to be equivalent. Boyden chamber invasion and wound-healing migration assays showed that MBD1-silenced cells were both more invasive and migratory compared with MeCP2-silenced cells. Finally, gene chip microarray analyses showed striking differences in the mRNA-expression profiles obtained from MeCP2- and MBD1-depleted cells relative to each other as well as when compared with control cells. The results of the present study suggest that MeCP2 and MBD1 silencing appear to affect cellular processes independently in vivo and that discrete sets of genes involved in cellular proliferation, apoptosis, invasion and migration are targeted by each protein.

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