Pharmacological inhibition of TREM1 attenuates patient derived xenograft models
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ashwin Ajith
PROVIDER: E-MTAB-13257 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We generated PDX models of aggressive NSCLC, which represent the DNA methylation features modelling of primary NSCLC
2021-11-24 | E-MTAB-10156 | biostudies-arrayexpress
Project description:Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting together secretomics and a TRanscriptional Activity CEll aRray (TRACER) to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of metastatic cell homing. Splenocytes from orthotopic mouse models of breast cancer were isolated to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased when cultured with D-SCM compared to healthy SCM (H-SCM) and unconditioned media controls. Our secretome analysis of D-SCM yielded secreted factor candidates that contribute to increased metastatic cell activity. In parallel, we identified active TFs within metastatic cells in response to the secreted factors using TRACER. We connected both data sets using MetaCore software to determine interactions between immune cell secreted factors and active metastatic cell TFs to narrow down functional secreted factor candidates that mediate metastatic cell homing. Haptoglobin was among the list of secreted factors and was validated in vitro as a key mediator of metastatic cell recruitment. Furthermore, we designed an implantable poly(lactide-co-glycolide) biomaterial scaffold as a mimic of the pre-metastatic niche to slowly release haptoglobin and demonstrate increased homing of metastatic cells to the scaffold in vivo. Taken together, our studies demonstrate a novel systems biology technique to identify functional paracrine signaling factors, which were validated to reveal mediators of metastatic cell homing.
2015-12-17 | PXD002051 | Pride
Project description:The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy across a population, but also study crucial aspects of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. The pathways most significantly altered included Protein Kinase A signaling, GNRH signaling, and sphingosine-1-phosphate signaling. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer 6 pairs of Patient-Derived Xenografts (PDX) were ananlyzed using RNA-seq for a total of 12 samples. Each pair consists of a treated and untreated PDX of ovarian cancer. Treated Ovarian cancer PDXs were treated with 4 weeks of a combination of carboplatin and taxol. RNA was isolated and converted to cDNA. RNA-seq was conductred on the Illumina HiSeq 2000 with 50 bp paired end sequencing
2015-06-17 | E-GEOD-58586 | biostudies-arrayexpress
Project description:To provide a snapshot of gene expression for the cancer models distributed by The Jackson Laboratory.
2021-12-17 | E-MTAB-9153 | biostudies-arrayexpress
Project description:To provide a snapshot of gene expression for the cancer models distributed by The Jackson Laboratory.
2021-12-17 | E-MTAB-9204 | biostudies-arrayexpress
Project description:Here, we analyzed patient-derived glioblastoma xenografts generated in the mouse brain that give rise to three different histological phenotypes: (i) a highly invasive phenotype (ii) a highly angiogenic phenotype and (iii) an intermediate phenotype. Cell type-specific transcriptomic profiles of tumor and stromal endothelial cells were analyzed to reveal phenotype-specific gene expression patterns and the reciprocal crosstalk between tumor and stromal endothelial cells. This part of the study contains the analysis of the stromal endothelial cells of the host mice. The analysis of the patient-derived tumor cells is found under E-MTAB-3948.
2016-06-30 | E-MTAB-3949 | biostudies-arrayexpress
Project description:To characterize and compare the transcriptomic expression profiles of shTREM1 and shControl HepG2 cells by microarray analysis.
2023-09-27 | E-MTAB-13249 | biostudies-arrayexpress
Project description:RNA-Seq and a species-specific mapping strategy were used to profile the human and mouse transcriptomes of tumour samples taken from 79 PDX models representing multiple cancer types (19 x breast, 37 x lung, 8 x colorectal, 7 x ovarian, 3 x endometrial, 2 x pancreatic, 2 x ampullary, 1 x leukaemia).
2016-03-01 | E-MTAB-3980 | biostudies-arrayexpress
Project description:Genomic changes in low and highly metastatic A549 cells were analyzed by 500K SNP arrays. A large number of genomic alterations were present in A549 cells but no significant differences were observed between the low or highly metastatic A549 cell lines. We generated a NSCLC line with highly increased propensity to form tumor nodules in murine lungs after intravenous injections. Extravasation and growth at a distant site are important parts of the metastatic process and we regarded these as a surrogate marker for in vivo aggressiveness and potential metastatic capability. A549 lung asdenocarcimona cell line with initially low metastatic potential was used for this purpose; these cells formed multiple small nodules in NOD/SCID mice after first i.v.-injection, round 1 (R1). Removal of tumor nodules from the lungs and subsequent re-injection led to a rapid increase in metastatic capacity. A highly aggressive phenotype which was stable over time was evident after three rounds (R3) of in vivo selection for the A549 cell line.
2013-02-21 | E-GEOD-44549 | biostudies-arrayexpress
Project description:Despite improvements in capabilities of proteomics technologies, the introduction of new plasma-based protein biomarkers for clinical use remains low. One reason is the cumbersome requirement to test thousands of protein candidates in follow-up quantitative verification studies. We sought to evaluate internal standard triggered parallel reaction monitoring (IS-PRM) in the context of biomarker verification by developing a method to quantify 5,176 peptides (1,314 proteins) as candidate biomarkers for early detection of breast cancer. Method performance was characterized in a response curve showing large linear range (4 orders of magnitude) and good repeatability (median CV 7.7%). The method was applied to pools of cancer and control human plasma, detecting 893 proteins and qualifying 164 candidates to advance for further evaluation. The method shows good quantitative performance, greatly expanding the capabilities for quantification of large numbers of proteins, and is well suited for large scale relative quantification of protein sets.
2022-06-29 | PXD028306 | Pride