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Pleiotrophin drives a pro-metastatic immune niche within the breast tumor microenvironment

ABSTRACT: Here, we evaluated the effect of Pleiotrophin (PTN) depletion on tumor microenvironment. For this, we utilized a mouse monoclonal antibody against PTN, 3B10. We tested its therapeutic efficacy in 2 mouse breast cancer models, 4T1 (orthotopic, 4th mammary fat pad) and MMTV-PyMT (genetic model). Tumors from control IgG(C44) treated and 3B10 treated mice were sent for RNA sequencing to evaluate transcriptional changes. Additionally, PTN was knocked down in E0771 and E0771-LG syngeneic breast cancer lines. To evaluate transcriptional changes due to PTN depletion, shCtrl and PTN KD cells from E0771 and E0771-LG were evaluated by RNA sequencing. Overall, our results from these 4 sets of experiments show that depletion or blocking PTN results in inflammation related transcript changes suggesting function of PTN in immune regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE200431 | GEO | 2023/02/16

REPOSITORIES: GEO

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Placental protein-1 (Plac1) modulates immune tolerance in mammary tumor cells

Project description:Plac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1). The RNeasy Mini Kit was used to purify total RNA from three independent cell culture samples for gene expression analysis. After isolation in parallel, 1 Î¼g of each of the total RNA from E0771/Scram or E0771/Shplac1 was pooled prior to microarray gene expression analysis. E0771/Scram was considered as control group in this experiment.

2016-02-24 | E-GEOD-78202 | biostudies-arrayexpress

Transcriptional changes induced by Lamin A/C downregulation in the nuclei of E0771 breast cancer cells

Project description:Major transcriptional changes (290 differentially expressed genes) take place upon downregulation of Lamin A/C in E0771 breast cancer cells

2021-06-02 | GSE151105 | GEO

Metabolomics-driven identification of biochemical mechanisms underlying the neuroprotective effects of pleiotrophin in a mouse model of Parkinson’s disease

Project description:Pleiotrophin (PTN) is a cytokine involved in nerve tissue repair processes, neuroinflammation and neuronal survival. PTN expression levels are upregulated in the nigrostriatal pathway of Parkinson’s Disease (PD) patients. We aimed to characterize the dopaminergic injury and glial activation in the nigrostriatal pathway of mice with transgenic Ptn overexpression in the brain (Ptn-Tg) after intrastriatal injection of the Parkinsonian toxin 6-hydroxydopamine (6-OHDA). The injection of 6-OHDA induced a significant decrease of the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and of the striatal TH contents in Wild type (Wt) mice. In contrast, these effects of 6-OHDA were blocked in Ptn-Tg mice. 6-OHDA injection did not cause robust changes in microglia but induced an exacerbated astrocytic response in Wt mice compared with Ptn-Tg mice. In metabolomics studies, we detected interesting metabolites that significantly discriminate the more injured 6-OHDA-injected Wt striatum and the more protected 6-OHDA-injected Ptn-Tg striatum. Particularly, we detected groups of metabolites, mostly corresponding to phospholipids, whose trends were opposite in both groups. In summary, the data confirm the neuroprotective effect of brain PTN overexpression in this mouse model of PD. New lipid-related PD drug candidates emerge from this study and the data presented here support the increasingly recognized “lipid cascade” in PD.

2021-06-01 | ST001810 | MetabolomicsWorkbench

Expression Array_Glioma_stem_cells

Project description:We evaluated the gene expression profiles of the 1228- and 0316-Glioma-initiating cells (GICs), as well as the original glioblastoma tissues from which they were derived, plus neural stem cells and normal brain tissues. Short- and long-term cultures of 0316-GICs (2 and 6 months, respectively) were also included in the analysis in order to evaluate the potential effects of in vitro culture duration on gene expression. Expressional changes by EZH2 depletion and DZnep treatment were also evaluated.

2011-06-18 | E-TABM-1121 | biostudies-arrayexpress

Whole-genome expression profiling of metastatic versus non-metastatic mammary tumors in MMTV-Wnt1 transgenic mice

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2019-07-26 | GSE84917 | GEO

ATAC-seq in control compared to ZEB1 knock-down MDA-MB-231 cells

Project description:Identification of open chromatin regions in wildtpye, control knock-down (shCtrl) and ZEB1 knock-down (shZEB1) human breast cancer MDA-MB-231 cells by ATAC(Assay for transposable-accessible chromatin)-seq.

2020-07-22 | E-MTAB-8264 | biostudies-arrayexpress

Transcription profiling of rat lacrimal gland samples from normal, sham and operated animals

Project description:Previous studies showed that loss of muscarinic parasympathetic input to the lacrimal gland (LG) leads to a dramatic reduction in tear secretion and profound changes to LG structure. In this study, we used DNA microarrays to examine the regulation of the gene expression of the genes for secretory function and organization of the LG. Long-Evans rats anesthetized with a mixture of ketamine/xylazine (80:10 mg/kg) underwent unilateral sectioning of the greater superficial petrosal nerve, the input to the pterygopalatine ganglion. After 7 days, tear secretion was measured, the animals were killed, and structural changes in the LG were examined by light microscopy. Total RNA from control and experimental LGs (n = 5) was used for DNA microarray analysis employing the U34A GeneChip. Control rat lacrimal gland samples representing a normal unoperated, a sham, and paired contralateral controls. Experimental LG samples representing paired and unpaired contralateral controls. Paired contralateral control LGs represent LG from the same animal, one side was operated and the other side unoperated.

2007-10-12 | E-GEOD-844 | biostudies-arrayexpress

Single-cell sequencing analysis of spinal cord motor neuron organoids (scMN-Organs)

Project description:Neonatal spinal cord tissues exhibit remarkable regenerative capabilities than adult tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans compared to adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs), and facilitated axonal outgrowth and regeneration of spinal cord organoids than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in rats with spinal cord injury (SCI). It suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

2024-03-01 | GSE255188 | GEO

O-linked Î²-N-acetylglucosamine (O-GlcNAc) acts as a glucose sensor to epigenetically regulate the insulin gene in pancreatic beta cells

Project description:We compare global gene expression changes in the Min6 cell line in response to altered glucose flux and pharmacological manipulation of the O-GlcNAc postranslational protein modification. Min6 cells were treated for 1hr in the following conditions: Low glucose (LG), high glucose (HG) and LG+GlcNAcstatin (LG+GNS). After treatment, total RNA was extracted and used for sequencing.

2016-02-22 | E-GEOD-74980 | biostudies-arrayexpress

Placental protein-1 (Plac1) modulates immune tolerance in mammary tumor cells

2016-02-24 | GSE78202 | GEO

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