Precociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. Here we present evidence that prostate cancer stem-like cells (CSC) can be found in histopathologically negative prostate draining lymph nodes (PDLN) in mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). PDLN-derived CSC were phenotypically and functionally identical to CSC obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. CSC derived from either PDLN or mPIN used the extracellular matrix protein Tenascin-C (TNC) to inhibit T cell receptor-dependent T cell activation, proliferation and cytokine production. Mechanistically, TNC interacted with 51 integrin on the cell surface of T cells, inhibiting reorganization of the actin-based cytoskeleton therein required for proper T cell activation. CSC from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in PDLN upon mPIN development. CXCR4 was critical for the development of PDLN-derived CSC, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Taken together, our work establishes a pivotal role for TNC in tuning the local immune response to establish equilibrium between disseminated nodal CSC and the immune system.
Tenascin-C Protects Cancer Stem-like Cells from Immune Surveillance by Arresting T-cell Activation.
Specimen part
View SamplesTo investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.
Age, Specimen part
View SamplesTranscriptome study of 2 Saccharomyces cerevisiae W303 derivatives, one carrying GFP (control) and one carrying aSyn-GFP
Different 8-hydroxyquinolines protect models of TDP-43 protein, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms.
Specimen part, Disease, Cell line
View SamplesTo assess the mechanism by which adult germ cells induce cbs-1 expression in the intestine at cold temperature, we performed transcriptome analysis of extruded germ lines from wild-type worms upon iff-1 knockdown or temperature increase Overall design: We extruded germ line of iff-1 RNAi-treated worms at 15°C and empty vector (EV) RNAi-treated worms at 20°C and compared to the germ line of EV RNAi-treated worms at 15°C.
Prostaglandin signals from adult germ stem cells delay somatic aging of <i>Caenorhabditis elegans</i>.
Specimen part, Subject
View SamplesBackground: Cancer stem cells are presumed to have virtually unlimited proliferative and self-renewal abilities and to be highly resistant to chemotherapy, a feature that is associated with overexpression of ATP-binding cassette transporters. We investigated whether prolonged continuous selection of cells for drug resistance enriches cultures for cancer stem-like cells.
Prolonged drug selection of breast cancer cells and enrichment of cancer stem cell characteristics.
Cell line, Treatment
View Samplesp63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
No sample metadata fields
View SamplesDHPM-thiones rescue Ab-mediated toxicity in a metal-dependent manner that strongly synergizes with clioquinol, a known metal-binding and cytoprotective compound. RNA-seq experiments reveal a modest, yet specific effect on metal-responsive genes that do not change with the inactive control compound. Overall design: Treatment of biological replicates with DMSO, 0.8 uM clioquinol, or 20 uM 10{3,3,1} (DHPM-thione) for ~6 hours prior to harvesting of cells and isolation of total RNA.
Dihydropyrimidine-Thiones and Clioquinol Synergize To Target β-Amyloid Cellular Pathologies through a Metal-Dependent Mechanism.
Cell line, Subject
View SamplesHepatocellular carcinoma (HCC) is ranked second in cancer-associated deaths worldwide. Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). It is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations.
Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesGastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed.
Genome-wide expression profile of sporadic gastric cancers with microsatellite instability.
No sample metadata fields
View SamplesIn order to identify the effects of Tcfeb overexpression on the kidney transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the double heterozygous KSP_CRE/KSP_Tcfeb 14 days old mice as compared to control KSP_CRE mice
Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling.
Specimen part
View Samples