Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA141273 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor). We used microarrays to detect differentially expressed genes in the TIC fraction compared to the non-TIC fraction of the same tumor
2011-05-28 | GSE29590 | GEO
Project description:The cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor). We used microarrays to detect differentially expressed genes in the TIC fraction compared to the non-TIC fraction of the same tumor Cells from each primary tumor were separated by FACS into TIC and non-TIC fractions and total RNA was extracted and hybridized on Affymetrix microarrays.
2011-05-28 | E-GEOD-29590 | biostudies-arrayexpress
Project description:Most solid tumors seem to be organized in a hierarchy in which only a fraction of cells, termed tumor-initiating cells (TICs), is capable of disseminating new tumors after transplantation into recipient mice. However, whether a single TIC can induce a tumor or whether it requires additional TICs or non-TICs for tumor initiation is not known. Here we show that injections of single CD24+:Jag1- cells from Her2/Neu+ mammary tumors into recipient mammary glands induced tumors at a frequency of 1/22. Single cell-derived secondary tumors exhibited histology, flow cytometry and global expression profiles that were indistinguishable from primary tumors. Thus, a single TIC can act cell autonomously to induce a tumor and therefore complete eradication of all TICs would be required to cure cancer. Total RNA obtained from primary MMTV-Neu tumors, secondary tumors generated by lin- cell transplantation, and secondary tumors generated by a single TIC, were used for microarray analysis to determine differentially regulated genes in the secondary tumors. Cluster analysis based on gene expression were then performed to assess tumor similarity
2011-05-30 | E-GEOD-29616 | biostudies-arrayexpress
Project description:Most solid tumors seem to be organized in a hierarchy in which only a fraction of cells, termed tumor-initiating cells (TICs), is capable of disseminating new tumors after transplantation into recipient mice. However, whether a single TIC can induce a tumor or whether it requires additional TICs or non-TICs for tumor initiation is not known. Here we show that injections of single CD24+:Jag1- cells from Her2/Neu+ mammary tumors into recipient mammary glands induced tumors at a frequency of 1/22. Single cell-derived secondary tumors exhibited histology, flow cytometry and global expression profiles that were indistinguishable from primary tumors. Thus, a single TIC can act cell autonomously to induce a tumor and therefore complete eradication of all TICs would be required to cure cancer.
2011-05-30 | GSE29616 | GEO
Project description:Tumor initiating cells (TIC) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potency, TICs are important for metastasis formation and involved in chemotherapy resistance. Here we explored the molecular pathways that enable the tumor initiating potential of a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45-, revealed a high tumorigenicity compared to CD24-CD90- cancer cells in colony formation assays as well as upon orthotopic transplantation into the mammary fad pad of mice. In addition, these orthotropically grown CD24+CD90+ TICs metastasized to the lungs. Upon cell sorting from primary tumors the transcriptome of TICs was compared with that of CD24-CD90- cancer cells by RNAseq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in CD24+CD90+TICs. Accordingly, TICs showed a high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on the colony morphology in 3D cell culture assays. Proteases have been frequently implicated in tumor growth and progression by shaping the extracellular environment and liberating growth factors, cytokines and chemokines. We conclude that CD24+CD90+ cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature that is likely to represent a functional hallmark of metastatic TICs of mammary carcinomas.
2016-08-17 | GSE75946 | GEO
Project description:Background: cancer cells rely on glycolysis as main ATP source (Warbürg effect). Tumor-initiating cells (TICs) are the fraction of cells that give raise and repopulate tumors. TICs are exposed to prolonged periods of oxygen and glucose deprivation (OGD), as they live in a hypoxic niche and they withstand prolonged lack of blood vessels during initial tumorigenesis or metastasis formation (avascular phase). Warbürg effect is energetically inefficient; we hypothesize that TICs might have differential metabolic features. Tumor eradication requires killing TICS; finding such features would have therapeutic implications. Methodology/principal findings: 106 MDA-MB-231 breast-cancer cells (hereafter Wt) were exposed for 5 weeks to 0.2% oxygen and 0.1g/l glucose, recovering 9 clones. Both flow-cytometry (50-fold enrichment in the CD24-/CD44+/CD133+ population) and xenografts in NOD/SCID mice using 100 cells (75% vs. 16% engraftment) suggest that OGD-resistant clones are true TICs (hereafter “TIC clones”). TIC clones showed a 30-fold higher replication and viability (BRDU incorporation, colony assay) than Wt. When exposed to OGD, ATP-production dropped 5-fold in WT, but was maintained in TIC clones by increasing 5-fold the fatty acid and oxygen consumption. These properties were explained by lack of upregulation of HIF-1 alpha and PDK1, as well as an increase in ATP-synthase. Analysis with metabolic inhibitors (2-deoxyglucose, antimycin-A) confirmed glycolysis and mitochondrial respiration as main routes of metabolism for Wt and TIC clones respectively. Metabolomics revealed that glutamine catabolism generated the NADPH required to quench reactive oxygen species generated during mitochondrial respiration in TIC clones. Glutamine deprivation or mitochondrial blockers were able to abrogate the viability of TIC clones. Conclusions/significance: the TIC-fraction of a cancer cell population withstands prolonged OGD by switching from the Warbürg effect to mitochondrial respiration. Targeting this metabolic feature abrogates the survival of TICs.
2015-12-13 | GSE37340 | GEO
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors.
2012-05-12 | GSE37946 | GEO
Project description:Undifferentiated pleomorphic sarcomas (UPS) are thought to harbor a small population of cells with unique capability of tumor initiation and maintenance. These tumor initiating cells (TICs) are regarded as the drivers of cancer progression. However, the evidence for this tumor initiating cell (TIC) concept is based on the xenotransplantation assays in mice and the clinical relevance of the TIC concept remains unclear in UPS. We hypothesized that the distinct properties of the TICs would be reflected in the clinical outcome if the TIC concept is relevant in UPS. Here we performed global gene expression profiling of TIC-enriched side population (SP) fractions and non-SP fractions sorted from 15 UPS primary samples. Ninety-three genes were differentially expressed in between SP fractions and non-SP fractions. The UPS TIC gene expression signature score summarizing expression of these genes was calculated for a gene expression data and was correlated with clinical outcome. In the 15 samples used to generate the signature, patients with high scores in the SP fractions were associated with worse survival. We then tested the two independent published datasets with gene expression data on bulk unsorted samples, assuming that the TIC gene expression would persist in the non-TICs. Patients with high scores had significantly worse metastasis-free survival in both datasets. The significance of the score remained significant even considering for the known prognostic factor of UPS. Thus, gene expression signature derived from UPS TICs predicts clinical outcome, suggesting the clinical relevance of the TIC concept in UPS.
2016-02-01 | GSE55973 | GEO
Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors. Neoadjuvant study of 50 HER2-positive breast cancer cases treated with trastuzumab-based chemotherapy pre-operatively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol. Pathologic response was assessed at the end of neoadjuvant treatment.
2012-05-11 | E-GEOD-37946 | biostudies-arrayexpress
Project description:Durable remissions following anti-B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell treatment of multiple myeloma (MM) are rare. Relapses occur when a small subset of MM tumor-initiating cells (TICs) survive treatment. MM cells expressing CD24 exhibit features of TICs. We developed CD24-CAR-T cells and tested their ability to eliminate MM TICs in vitro and in vivo.
2023-03-13 | GSE226956 | GEO