A facile method for generating tumorigenic cancer stem cell spheroids from diverse cancer cell lines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA418170 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6286151.fastq.gz | Fastqsanger.gz | |||
| SRR6286152.fastq.gz | Fastqsanger.gz | |||
| SRR6286153.fastq.gz | Fastqsanger.gz | |||
| SRR6286154.fastq.gz | Fastqsanger.gz |
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Project description:Although cancer stem cells (CSCs) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of patient-derived diverse CSCs. Here, we developed a functional polymer thin film (PTF) platform that promotes conversion of human cancer cell lines to highly tumorigenic spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular spheroids within 24 hours, with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed an enormous increase in the expression of CSC-associated genes and acquired dramatically increased drug resistance compared with monolayer-cultured controls. These spheroids also showed greatly enhanced xenograft tumor-forming ability and metastasis capacity in nude mice. By enabling the generation of tumorigenic spheroids as a patient-derived CSC substitute, the surface platform described here will likely contribute to CSC-related basic research and drug development.
2018-10-31 | GSE106848 | GEO
Project description:Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the beta-catenin pathway. A parallel increase in the expression levels of beta-catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that beta-catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated beta-catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of beta-catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population. Different gene profiles were observed in ovarian cancer spheroids versus ovarian cancer monolayers. Nine samples were analyzed in triplicate. Each group is a reference.
2014-01-03 | E-GEOD-53759 | biostudies-arrayexpress
Project description:Microarry based whole genome expression analysis was done for the more tumorigenic CaSki spheroids cultures and the less tumorigenic CaSki adherent cultures to identify signaling mechanisms that vary between the two populations. Subsequent to this, an independent array was done to characterize the differences in gene expression between the cancer stem cell-like Lin-CD66+ and the bulk Lin- CD66- cells isolated from primary human cervical carcinomas. The second array was custom-designed and had genes implicated in stemness, epithelial differentiation, signaling pathways implicated in stemness (Notch and Wnt) and cell cylce-regulation. Microarray analysis of CaSki cell line grown as spheroids and adherent conditions
2011-06-09 | E-GEOD-26417 | biostudies-arrayexpress
Project description:Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the β-catenin pathway. A parallel increase in the expression levels of β-catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that β-catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated β-catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of β-catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.
2014-01-03 | GSE53759 | GEO
Project description:Chromatogram library generated of pooled sample. Coculture spheroids formed from fibroblast and colon cancer cell lines, and monoculture spheroids formed from the colon cancer cell line HCT116.
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Project description:Hyphomicrobium facile subsp. facile DSM 1565 genome sequencing
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Project description:microRNAs in ovarian cancer cell spheroids
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Project description:Background: Mesenchymal stem cells (MSC) derived from human embryonic stem cells (hESC), named EMSC here, have been found efficacious in animal models of autoimmune, inflammatory, and degenerative diseases. However, all the EMSC derivation methods reported so far are in two-dimensional (2D) culture systems, which are of low efficiency and high cost, difficult for large-scale production for research and therapeutic applications. Methods: We established a 3D system that allowed differentiation of hESC spheroids into MSC spheroids (EMSCSp) following treatment with BMP4 and A8301 for 5 days and subsequent culture in a MSC medium for about 15 days. All the procedures were conducted in one vessel without intermediate passaging. Results: EMSCsp cells were efficiently derived from hESC spheroids within 20 days in the 3D culture system, which could be scaled up from a small culture vessel to a 100-ml plastic bag. EMSCSp could further differentiate into spheroids of chondrocytes or adipocytes. EMSCSp could also reattach and form a 2D-monolayer culture (EMSCSp-ML). Compared to EMSC differentiated in monolayer, EMSCSp-ML had faster proliferation and higher yield, and developed less apoptosis and slower senescence. EMSCSp-ML also retained immune-modulatory effects in vitro and therapeutic effects on two mouse models of colitis. Conclusions: The 3D method provides a simple and economic system for large-scale production of EMSC as an unlimited source of the therapeutically promising cells.
2018-07-03 | GSE93218 | GEO
Project description:Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression in vivo. However, it remains unclear how spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving cancer. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models which lack the major cell-cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. Using flow cytometry, we show that the expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 to sense changes in static extracellular matrix stiffness and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.
2024-03-28 | GSE262142 | GEO
Project description:Gene profile in ovarian cancer cell spheroids
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