Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA224091 | ENA |
REPOSITORIES: ENA
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Project description:The erythropoietin (EPO) hormone induces red blood cell production and its recombinant form is the most prescribed drug for the treatment of anemia, including that arising in cancer patients. Based on randomized trials showing that EPO administration to cancer patients result in a decreased survival, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer we found that EPO promoted tumorigenesis by activating JAK/STAT signaling specifically in breast tumor initiating cells (TICs) and promoting their self-renewal. Moreover, we define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and demonstrate a potential application of EPO pathway inhibition in breast cancer therapy. reference x sample
2014-05-31 | E-GEOD-51433 | biostudies-arrayexpress
Project description:The erythropoietin (EPO) hormone induces red blood cell production and its recombinant form is the most prescribed drug for the treatment of anemia, including that arising in cancer patients. Based on randomized trials showing that EPO administration to cancer patients result in a decreased survival, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer we found that EPO promoted tumorigenesis by activating JAK/STAT signaling specifically in breast tumor initiating cells (TICs) and promoting their self-renewal. Moreover, we define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and demonstrate a potential application of EPO pathway inhibition in breast cancer therapy.
2014-05-31 | GSE51433 | GEO
Project description:Using a syngeneic p53 null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified by limiting dilution transplantation as well as in vitro mammosphere and clonogenic assays a Lin-CD29HighCD24High subpopulation of tumor-initiating cells. Differentially expressed genes in the Lin-CD29HighCD24High mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. Keywords: tumor-initiating cells
2008-06-27 | GSE8863 | GEO
Project description:The differentiation of stem-like cells of tumors may contribute to the cellular heterogeneity of breast cancers. We report the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. We identify epithelial tumor initiating cells (ETIC) that expresses lineage markers of both basal and luminal mammary cell lineages and retains the potential to generate heterogeneous tumors similar to the tumor of origin from even single cells. ETIC can progress through a Rho associated coil-coil protein kinase 1 (ROCK1) dependent, epithelial to mesenchymal transition to generate a second cell type capable of initiating tumors of limited heterogeneity. The propagation of ETIC will increase the opportunities for identifying new therapeutic compounds that may inhibit or prevent progression of some types of breast cancer. These data compare the gene expression pattern of ETIC and MTIC. Total RNA obtained from ETIC and MTIC cells, allowing the comparison of gene expression patterns and the selection of potential targets.
2012-09-01 | E-GEOD-33433 | biostudies-arrayexpress
Project description:Using established human CRC cell lines, we showed that progastrin expression were enriched under conditions that promote tumor-initiating cells (TIC) self-renewal.
2016-06-29 | E-MTAB-3215 | biostudies-arrayexpress
Project description:Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote their growth and progression. TCF3 (also known as TCF7L1) is a member of the TCF/LEF transcription factor family that is central in regulating epidermal and embryonic stem (ES) cell identity. We found that TCF3 is highly expressed in poorly differentiated human breast cancers, preferentially of the basal-like subtype. This suggested that TCF3 is involved in the regulation of breast cancer cell differentiation state and tumorigenicity. Silencing of TCF3 dramatically decreased the ability of breast cancer cells to initiate tumor formation, and led to decreased tumor growth rates. In culture, TCF3 promotes the sphere formation capacity of breast cancer cells and their self-renewal. We found that in contrast to ES cells, where it represses Wnt-pathway target genes, TCF3 promotes the expression of a subset of Wnt-responsive genes in breast cancer cells, while repressing another distinct target subset. In the normal mouse mammary gland Tcf3 is highly expressed in terminal end buds, structures that lead duct development. Primary mammary cells are dependent on Tcf3 for mammosphere formation, and its overexpression in the developing gland disrupts ductal growth. Our results identify TCF3 as a central regulator of tumor growth and initiation, and a novel link between stem cells and cancer. Cells infected with different shRNA vectors were either untreated, treated with control or Wnt3A condition medium. Condition medium treatments were done in biological repeats.
2012-10-23 | E-GEOD-38893 | biostudies-arrayexpress
Project description:Introduction: Tumor initiating cells (TICs) are being extensively studied for their role in tumor etiology, maintenance and resistance to treatment. The isolation of TICs has been limited by the scarcity of this population in the tissue of origin and because the molecular signatures that characterize these cells are not well understood. Herein, we describe the generation of TIC-like cell lines by ectopic expression of the OCT4 transcription factor (TF) in primary breast cell preparations. Methods: OCT4 cDNA was over-expressed in four different primary human mammary epithelial (HMEC) breast cell preparations from reduction mammoplasty donors. OCT4-transduced breast cells (OTBCs) generated colonies (frequency ~0.01%) in self-renewal conditions (feeder cultures in human embryonic stem cell media). Differentiation assays, immunofluorescence, immunohistochemistry, and flow cytometry were performed to investigate the cell of origin of OTBCs. Serial dilutions of OTBCs were injected in nude mice to address their tumorigenic capabilities. Gene expression microarrays were performed in OTBCs, and the role of downstream targets of OCT4 in maintaining self-renewal was investigated by knock-down experiments. Results: OTBCs overcame senescence, overexpressed telomerase, and down-regulated p16INK4A. In differentiation conditions, OTBCs generated populations of both myoepithelial and luminal cells at low frequency, suggesting that the cell of origin of some OTBCs was a bi-potent stem cell. Injection of OTBCs in nude mice generated poorly differentiated breast carcinomas with colonization capabilities. Gene expression microarrays of OTBC lines revealed a gene signature that was over-represented in the claudin-low molecular subtype of breast cancer. Lastly, siRNA-mediated knockdown of OCT4 or downstream embryonic targets of OCT4, such as NANOG and ZIC1, suppressed the ability of OTBCs to self-renew. Conclusions: Transduction of OCT4 in normal breast preparations lead to the generation of cell lines possessing tumor initiating and colonization capabilities. These cells developed high-grade, poorly differentiated breast carcinomas in nude mice. Genome-wide analysis of OTBCs outlined an embryonic TF circuitry that could be operative in TICs, resulting in up-regulation of oncogenes and loss of tumor suppressive functions. These OTBCs represent a patient-specific model system for the discovery of novel oncogenic targets in claudin-low tumors. 12 cell lines
2011-08-16 | E-GEOD-26539 | biostudies-arrayexpress
Project description:The differentiation of stem-like cells of tumors may contribute to the cellular heterogeneity of breast cancers. We report the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. We identify epithelial tumor initiating cells (ETIC) that expresses lineage markers of both basal and luminal mammary cell lineages and retains the potential to generate heterogeneous tumors similar to the tumor of origin from even single cells. ETIC can progress through a Rho associated coil-coil protein kinase 1 (ROCK1) dependent, epithelial to mesenchymal transition to generate a second cell type capable of initiating tumors of limited heterogeneity. The propagation of ETIC will increase the opportunities for identifying new therapeutic compounds that may inhibit or prevent progression of some types of breast cancer. These data compare the gene expression pattern of ETIC and MTIC.
2012-09-01 | GSE33433 | GEO
Project description:Tumor-initiating cells with reprogramming plasticity and/or de-differentiation attributes have been thought to initiate primary tumor development as well as to regenerate secondary tumors in metastatic organs; however, the molecular mechanisms are not fully understood. We previously found that breast tumor-initiating cell marker, CD44, directs multicellular aggregation and cluster formation of circulating tumor cells (CTCs), which further enhance stemness and survival of such cells, enabling metastatic colonization to the lungs. To further elucidate the molecular network underlying CTC cluster formation, we performed global proteomic profiling and discovered that the tetraspanin protein CD81, which is normally enriched in exosomes (small extracellular vesicles), is a new driver of cancer initiation and metastasis as a facilitator and target of CD44. Loss of CD81 compromises tumorigenicity and mammosphere formation of triple negative breast cancer (TNBC) cells. Assisted by machine learning-based algorithms and mutagenesis approach, we found that CD81 interacts with CD44 on the cellular membrane through their extracellular regions. Notably, genetic knockout of CD44 or CD81 results in loss of both CD81 and CD44 in secreted exosomes, a state which abolishes exosome-induced self-renewal of recipient cells, such as mammosphere formation. In addition, RNA sequencing analysis showed that CD81 knockdown up-regulates expression of a cell differentiation marker, SEMA7a, whose down-regulation partially rescues mammosphere formation inhibition by CD81 depletion. Clinically, CD81 expression was observed in >80% of CTCs and specifically enriched and co-expressed along with CD44 in clustered CTCs of breast cancer patients. Mimicing the phenotypes of CD44 deficiency, loss of CD81 also inhibited tumor cell aggregation and lung metastasis of TNBC in both human and mouse tumor models, supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights a new driving role of CD81 in cancer exosome-induced stemness, clustered CTCs, and metastasis initiation of TNBC, reported for the first time to our knowledge.
2022-10-18 | PXD029529 | JPOST Repository
Project description:Breast cancer stem cells (bCSCs) have been implicated in tumor progression and therapeutic resistance; however, the molecular mechanisms that define bCSC-state are unclear. We have performed concurrent human miRNome-wide gain- and loss-of-function screens to identify switcher miRNAs controling the choice between bCSC self-renewal and differentiation. These analysis enlightened miR-600 whose silencing resulted in bCSC expansion. Mechanistically, miR-600 targets the stearoyl desaturase 1 (SCD1), an enzyme required to produce active, lipid-modified WNT proteins. To explore further miR-600 interactions and WNT-pathway, SUM159 cell line constructions were made and FACS-sorted to select the bCSCs. We compared gene expression profiles from native, miR-600 'over-expressed', miR-600'knock-down' and siSCD1 bCSCs. We showed that in the absence of miR-600, WNT signaling is maintained active and promotes self-renewal, whereas overexpression of miR-600 inhibits the production of active WNT proteins and promotes bCSC differentiation. These findings highlight a miR-600-centered signaling network that governs bCSC-fate decision and influences tumor progression.
2020-08-25 | E-MTAB-5393 | biostudies-arrayexpress