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GSE69402
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We report a novel mechanism of the interaction between perivascular cell and TAMs in promoting metastasis through the IL-33-ST2-dependent pathway. IL-33 was the highest up-regulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Il33-/- deficient mice showed impaired TAM recruitment and metastasis. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibited TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocked PDGF-BB-induced TAM recruitment and metastasis. High IL-33 in human cancers correlated with poor survival prognosis. These findings shed novel mechanisms of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.
Publication Title
Molecular mechanisms of IL-33-mediated stromal interactions in cancer metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Anti-PDGF agents are routinely used as a key component in front-line therapy for the treatment of various cancers. However, molecular mechanisms underlying their impact on vascular remodeling in relation to the dose issue remain poorly understood. Here we show that in high PDGF-BB-producing tumors, anti-PDGF drugs significantly inhibited tumor growth and metastasis by preventing pericyte (PC) loss and vascular permeability. Surprisingly, the same anti-PDGF-BB drugs promoted tumor cell dissemination and metastasis in PDGF-BB-low-producing or negative tumors by ablating PCs from tumor vessels. At the molecular level, we show that the PDGFR- signaling pathway in PCs mediated the opposing effects and persistent exposure of PCs to PDGF-BB led to marked downregulation of PDGFR-. Inactivation of the PDGFR- signaling system led to decreased levels of integrin 11, resulted in impaired adhesion of PCs to collagen I, IV and laminin, two principal extracellular matrix components in blood vessels for interaction with these integrins. Our data suggest that tumor PDGF-BB levels may serve as an important biomarker for selection of tumor-bearing hosts for beneficial therapy and unsupervised practice of this group of drugs could potentially promote tumor invasion and metastasis.
Publication Title
Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We used microarrays to detail the gene expression profile during WAT -beige transition by treatment of beta adrenergic receptor agonist .
Publication Title
Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Vascular pericytes, an important cellular component, in the tumor microenvironment, are often associated with tumor vasculatures and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte fibroblast transition (designated as PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that the PDGF-BB-PDGFR signaling promotes PFT in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFR ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, i.e., TN-AP-CreERT2:R26R-tdTomato and NG2:R26R-tdTomato, shows that PFT cells gains stromal fibroblast and myofibroblast markers in tumors. Importantly, co-implantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells (CTCs) and metastasis. Our findings reveal a novel mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT and thus targeting PFT may offer a new treatment option of cancer metastasis.
Publication Title
Pericyte-fibroblast transition promotes tumor growth and metastasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes
Publication Title
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells express different sets of receptor type tyrosine kinases. These receptor kinases may be activated through autocrine or paracrine mechanisms. Fibroblasts may modify the biologic properties of surrounding cancer cells through paracrine mechansms.
Publication Title
The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
NextSeq 500
Description
Podocytes are highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria and glomerulosclerosis. Studies into podocyte biology and disease have previously relied on conditionally immortalised cell lines due to the non- proliferative nature of this cell type. Here we describe an advanced model to study both podocyte and glomerular biology using isolated glomeruli from kidney organoids derived from human pluripotent stem cells. Overall design: Gene expression profiling of day three 17, 21 and 26 day kidney organoid derived glomeruli respectively with heterzygous genotype for BFP tagged MAFB; gene expression profiling of three day 25 kidney organoid derived glomeruli; gene expression profiling of three organoid-derived podocytes grown out for 3 days from day 25 kidney organoid derived glomeruli.
Publication Title
3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to evaluate the effect of SRPIN803 on gene expression in ARPE-19 cells.
Publication Title
Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological Angiogenesis of Macular Degeneration in Mice.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: To determine the effects of age and topographic location on gene expression in human neural retina.
Publication Title
Effects of aging and anatomic location on gene expression in human retina.
Sample Metadata Fields
Sex, Age
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction regimens lead to enhanced stress resistance and extended lifespan in many species through the regulation of fasting and/or diet responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Several studies have implicated that the nervous system is involved in the regulation of longevity. However, it remains largely unknown whether the nervous system contributes to the regulation of lifespan and/or stress resistance elicited by fasting. In this study, we first investigated the role of the nervous system in fasting-elicited longevity and stress resistance. We found that lifespan extension in Caenorhabditis elegans caused by an intermittent fasting (IF) regimen was suppressed by functional defects in sensory neurons. The IF-induced longevity was also suppressed in a mutant that lacks the enzyme required for the synthesis of an amine neurotransmitter, octopamine (OA), which acts in the absence of food, i.e., under fasting conditions. Although OA administration did not significantly extend the lifespan, it enhanced organismal resistance to oxidative stress. This enhanced resistance was suppressed by a mutation of the OA receptors, SER-3 and SER-6. Moreover, we found that OA administration promoted the nuclear translocation of DAF-16, the key transcription factor in fasting responses, and that the OA-induced enhancement of stress resistance required DAF-16. Altogether, our results suggest that OA signaling, which is triggered by the absence of food, shifts the organismal state to a more protective one to prepare for environmental stresses.
Publication Title
Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans.
Sample Metadata Fields
Specimen part
View Samples