The leading cause of death in human patients with metastatic renal cell carcinoma (RCC) and malignant cancer in general is the dissemination of the primary tumor to secondary sites. The mechanisms by which RCC colonize the lung microenvironment during metastasis remain largely unknown. To investigate the mechanisms of lung colonization by tumor cells, we grafted human RCC cells with different lung metastatic activities in mice. Gene expression profiling of the mouse lung stromal compartment revealed a gene signature enriched for neutrophil-specific functions, induced preferentially by poorly metastatic cells. Analysis of the gene expression patterns in tumor cells and clinical specimens showed an inverse correlation between metastatic activity and the levels of a number of chemokines, including CXL5 ad IL8. Enforced depletion of CXCL5 and IL8 in tumor cells allowed us to establish a functional link between lung neutrophil infiltration, the secretion of chemokines by cancer cells and metastatic activity. Finally, we showed that human neutrophils displayed a higher cytotoxic activity toward poorly metastatic cells relative to highly metastatic cells. Together, these results support a model in which neutrophils recruited to the lung by tumor-secreted chemokines build an antimetastatic barrier and loss of those neutrophil chemokines in tumor cells is a critical rate-limiting step during lung metastatic seeding.
Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic response during renal cell carcinoma progression.
Specimen part
View SamplesMicroarray experiments were performed using FAC-sorted young photoreceptors to analyze their transcriptome in comparison to remaining retinal cells at same developmental stage and retinal progenitors.
Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina.
Specimen part
View SamplesIn a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the -secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity.
Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice.
Sex, Age
View SamplesWe analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Time
View SamplesBackground: Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids.
Activation of sterol-response element-binding proteins (SREBP) in alveolar type II cells enhances lipogenesis causing pulmonary lipotoxicity.
Specimen part
View SamplesChromatin architectural protein NSBP1/HMGN5 belongs to the family of HMGN proteins which specifically interact with nucleosomes via Nucleosome Binding Domain, unfold chromatin and affect transcription. Mouse NSBP1 is a new and uncharacterized member of HMGN protein family. NSBP1 is a nuclear protein which is localized to euchromatin, binds to linker histone H1 and unfolds chromatin.
The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription.
No sample metadata fields
View SamplesWe report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Resolving Heart Regeneration by Replacement Histone Profiling.
No sample metadata fields
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