Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

ABSTRACT: Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment that supports tumorigenesis. Here we found that prostate tumors are strongly infiltrated by TAMs expressing the C-X-C chemokine receptor type 2 (CXCR2). Pharmacological blockade of the CXCR2 receptor by a selective antagonist promoted the re-education of TAMs towards a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Ptenpc-/-; Trp53pc-/- mice preferentially differentiatied in TNFα-releasing pro-inflammatory macrophages leading to senescence induction and tumor inhibition. Moreover, tumor cells harboring PTEN deletion were more sensitive to TNFα-induced senescence, when compared to PTEN WT tumors, due to increased levels of TNFR1. Our results identify TAMs as a target in prostate cancer therapy and describe a novel therapeutic strategy based on CXCR2 blockade to harness the anti-tumorigenic potential of macrophages against this disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE124058 | GEO | 2019/12/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

Project description:Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment that supports tumorigenesis. Here we found that prostate tumors are strongly infiltrated by TAMs expressing the C-X-C chemokine receptor type 2 (CXCR2). Pharmacological blockade of the CXCR2 receptor by a selective antagonist promoted the re-education of TAMs towards a pro-inflammatory phenotype. In vitro gene expression profiling revealed that CXCL2 promotes a pro-tumorigenic (M2-like) functional state in macrophages.

2019-06-03 | GSE125273 | GEO

RNA seq of prostate gland from WT, PTEN pc -/- and PTEN pc-/-;P53 -/- mice

Project description:Acute Pten loss initiates prostate tumorigenesis characterized by cellular senescence response. Senescent cells secrete a variety of pro inflammatory factors in the tumor microenvironment, which can support the survival, outgrowth and migration of tumor cells. Here we examine cytokines and cytokines-related factors gene expression in Ptenpc-/- senescent and in Ptenpc-/-; Trp53pc-/- non senescent tumors. RNAseq analysis confirmed the presence of cytokines, which were specifically up- and down-regulated in Ptenpc-/- senescent tumors (“core-SASP”) we also found a number of upregulated secreted factors that were “senescence-unrelated” both present in both Ptenpc-/- and Ptenpc-/-; Trp53pc-/- tumors.

2020-10-09 | E-MTAB-9624 | biostudies-arrayexpress

Complete LKB1 loss results in lethal metastatic prostate cancer

Project description:In order to identify the contribution of Lkb1 loss to Pten driven prostate cancer progression, we engineered a prostate conditional mutant mice in which was induced the loss of Lkb1 in combination with heterozygous loss of the prostate tumor suppressor Pten (Ptenpc+/- Lkb1pc-/-). This mouse model developed metastatic prostate squamous cell carcinoma. We compared this tumor type with the adenocarcinomas developed in Ptenpc-/- Lkb1pc+/+ mice. We carried out microdissection and RNA extraction of tumor tissues embedded in paraffin of Ptenpc+/- Lkb1pc-/- and Ptenpc-/- Lkb1pc+/+. To distinguish between early and late phenotype of prostate squamous cell carcinoma, we compared Ptenpc+/- Lkb1pc-/- tumor tissues collected at the age of six and ten months of age among them and with Ptenpc-/- Lkb1pc+/+ mouse prostate tissue.

2020-03-20 | GSE133837 | GEO

Single cell sequencing analysis of senescence in Mus musculus prostate cancer models

Project description:Acute Pten loss initiates prostate tumorigenesis characterized by cellular senescence response. Here we examine the cellular senescence response in epithelial individual cells, by single-cell RNA sequencing (scRNAseq) in Ptenpc-/- and Ptenpc-/-; Timp1-/- GEMMs. ScRNAseq analysis determines a cluster of senescent cells expressing the senescence-related genes. A significant positive correlation is observed between the senescence score and Bcl2 expression. This provides the rational for targeting senescent cells using Bcl2 inhibitor.

2020-10-09 | E-MTAB-9578 | biostudies-arrayexpress

Prostate specific Pten deletion, Pten-Smad4 deletion, and Pten-p53 deletion

Project description:We used microarrays to detail the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Ptenpc-/- anterior prostates, Ptenpc-/-Smad4pc-/- and Ptenpc-/- anterior prostates, Ptenpc-/-p53pc-/- and Ptenpc-/- anterior prostates at 15 weeks of age. Prostate-specific Pten deletion (Ptenpc-/-) results in prostate intraepithelial neoplasia (PIN) which, following a long latency, can progress to high-grade adenocarcinoma, albeit with minimally invasive and metastatic features. To understand this feeble progression phenotype, we conducted transcriptome comparison of five Ptenpc-/- PIN relative to three wild-type anterior prostate. Moreover, Ptenpc-/-Smad4pc-/- progress to metastasis, while Ptenpc-/-p53pc-/- not progress to metastasis. To understand this phenotype difference, we conducted transcriptome comparison of five Ptenpc-/-Smad4pc-/-to five Ptenpc-/- prostate tumor, and three Ptenpc-/-p53pc-/- to five Ptenpc-/- tumor.

2010-11-05 | E-GEOD-25140 | biostudies-arrayexpress

Gene expression analysis of CD11b+Gr-1+ myeloid cells and epithelial cells purified from Pten KO prostate tumours

2014-06-13 | GSE58413 | GEO

Gene expression analysis of CD11b+Gr-1+ myeloid cells and epithelial cells purified from Pten KO prostate tumours

Project description:Gr-1+ myeloid cells are recruited in prostate conditioanal Pten null tumours (Ptenpc-/-). To identify the secreted factors that may be released by Gr-1+ cells and epithelial cells in the tumour microenvironment, we compared, by gene expression analysis, the cytokine profile of Gr-1+ myeloid cells sorted from Ptenpc-/- tumours with the profile of immune cell-depleted Ptenpc-/- epithelial cells. qRT-PCR validation for IL-10, IL1rn, IL-1α, IL-6, VEGF, TNFα, CXCL1, CCL2 and CXCL12 was also performed. Pten pc-/- 8 weeks old mice were sacrificed and whole prostates were isolated and processed to single cell suspension. mRNA from sorted Gr-1+ myeloid cells and epithelial cells was used for gene expression analysis. Cells sorted from 3 mice/each experiment were pulled together. 2 independent experiments were performed.

2014-06-13 | E-GEOD-58413 | biostudies-arrayexpress

Transcriptomic profiling and analyses of murine prostate tumours

Project description:RNA sequencing was performed on wildtype prostate tissues and tumours from mice with prostate-specific deletion of Pten (Ptenpc-/-) and oncogenic activation of ß-catenin (Ctnnb1pcex3(Δ)/+ Ptenpc-/+ , Ctnnb1pcex3(Δ)/+, Mock and ADT treated Ctnnb1Nkx3-1CreERT2(ex3)Δ/+ Pten Nkx3-1CreERT2(ex3)Δ+/-).

2022-08-20 | GSE136080 | GEO

Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

Project description:Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

| PRJNA510636 | ENA

Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

Project description:Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

| PRJNA515730 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data