The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (Core OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.
The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesVSV-M2 is recognized by cytosolic RIG-I. Notably, 5'-triphosphate RNA molecules derived from either viral RNA or from the synthetically produced 3pRNA can also induce RIG-I activation. MDA5 stimulation is achieved using complexed poly(I:C), a synthetic analog of viral dsRNA.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesBrain endothelial cells are an essential part of the blood-brain-barrier (BBB) and, as such, are exposed to proinflammatory mediators as well as danger signals during infections. They might function as decisive cells mediating RNA virus- and IFN-mediated sickness behavior.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Specimen part, Treatment, Time
View SamplesTranscript profiling analysis of csn4-1 light grown mutant seedlings compared to wild type using Arabidopsis ATH1 GeneChip array
Characterization of the VIER F-BOX PROTEINE genes from Arabidopsis reveals their importance for plant growth and development.
No sample metadata fields
View SamplesTo gain a deep understanding of mRNA turnover dynamics in mammalian cells, we pulse labeled newly synthesized RNA in 3t3 cells for 2 h with 4sU. RNA samples were fractionated into the newly synthesized and pre-existing fractions. Both fractions and the total RNA sample were analyzed by mRNA sequencing. We estimated mRNA half-lives based on the ratios of newly synthesized RNA/total RNA ratio and the preexisting RNA/total RNA.
Global quantification of mammalian gene expression control.
No sample metadata fields
View SamplesGene expression of periphereal blood lymphocytes (PBLs) of patients with metastatic renal cell carcinoma pre and post immunotherapy was accessed and pre therapy gene expression was compared to PBL gene expression of healthy volunteers
Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.
Specimen part, Disease, Disease stage
View SamplesBrain perivascular cells have been recently identified as new mesodermal cell type of the human brain.
Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.
Specimen part
View SamplesConditional ablation of Ezh2 in the neural crest lineage results in loss of the neural crest-derived mesenchymal derivatives. In this data sheet we determine gene expression analysis in Ezh2lox/lox and Wnt1Cre Ezh2lox/lox in E11.5 mouse BA1 cells.
Ezh2 is required for neural crest-derived cartilage and bone formation.
Specimen part
View SamplesPurpose:
Sequential gene expression profiling during treatment for identification of predictive markers and novel therapeutic targets in chronic lymphocytic leukemia.
Treatment
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