Immunoprofiling of prostate cancer infiltrate
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ABSTRACT:
PROVIDER: PRJNA644438 | ENA |
REPOSITORIES: ENA
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Project description:Tumor associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa) but are still poorly described in this context. Here we applied high dimensional single-cell RNA-seq to profile the transcriptional landscape of TAMs in PCa. We identified a subset of tumor infiltrating macrophages that shows a dysregulation in transcriptional pathways associated with lipid metabolism. In human and mouse models of PCa this subset of macrophages expresses the scavenger receptor MARCO and is characterized by accumulation of lipid droplets. We identified a gene signature derived from MARCO-expressing TAMs that correlates with PCa progression and is associated with shorter disease-free survival. Mechanistically, we observed that lipid accumulation in TAMs is promoted by the secretome of cancer cells. Lipid-loading confers to tumor-conditioned macrophages the capability to promote cancer cell migration mediated by CCL6. Importantly, administration of high fat diet to tumor-bearing mice raises lipid accumulation in TAMs and affects their transcriptional profile. Finally, we demonstrate that the accumulation of lipids in macrophages is dependent on MARCO expression and we show that MARCO blockade hinders tumor growth and invasiveness in models of advanced PCa. Our findings provide evidence that lipid-loaded TAMs represent a new therapeutic target in PCa.
2022-01-12 | GSE153892 | GEO
Project description:The development of autonomic nerve fibres in the tumour microenvironment is a pivotal event that regulates prostate cancer initiation and dissemination, but how nerves emerge in tumours is presently unknown. Here we show that Doublecortine-expressing (DCX+) neural precursors from the central nervous system (CNS) infiltrate prostate tumours and differentiate into neo-neurons that contribute to tumour development. In human primary prostate tumours and transgenic mouse cancer tissues, the density of DCX+ neural progenitors is strongly associated with tumour aggressiveness, invasion and recurrence. We found that DCX+ neural precursors egress from the subventricular zone, a neurogenic area of the CNS, and circulate in the blood to reach the tumour where they initiate neurogenesis. Hence, the DCX+ cells in prostate tumour can differentiate into neurons ex vivo and build up a tumour-associated neural network in vivo. Selective genetic depletion of DCX+ cells in mice significantly inhibits the early phases of prostate cancer development, whereas orthotopic transplantation of DCX+ cells purified from prostate tumour or brain tissues promotes tumour growth and cancer cell dissemination. These results unveil a unique crosstalk between the CNS and the tumour that drives a process of neurogenesis necessary for prostate cancer development, and indicate a novel neural element of the tumour microenvironment as a potential target for cancer treatment.
2019-05-16 | E-MTAB-7727 | biostudies-arrayexpress
Project description:Prostate cancer cells (PC3) were treated with purified human recombinant CRISP3 protein or vehicle control for 4 hours before whole cell protein extraction
2020-07-15 | PXD009609 | JPOST Repository
Project description:Prostate cancer is the second most occurring cancer in men worldwide, and with the advances made with screening for prostate-specific antigen, it has been prone to early diagnosis and over-treatment. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. The model includes pathways such as androgen receptor, MAPK, Wnt, NFkB, PI3K/AKT, MAPK, mTOR, SHH, the cell cycle, the epithelial-mesenchymal transition (EMT), apoptosis and DNA damage pathways. The final model accounts for 133 nodes and 449 edges. We applied a methodology to personalise this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients, using TCGA and GDSC datasets.
2022-06-22 | MODEL2106070001 | BioModels
Project description:Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. In DD patients, the skin is frequently affected, characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. Using immunoprofiling with NanoString technology we demonstrate enhanced expression of Th-17-related genes and cytokines in five DD patients. We prove that targeting the IL-23/-17 axis in DD with monoclonal antibodies is an effective and safe therapy in DD patients, leading also to significant clinical improvement.
2023-09-23 | GSE222043 | GEO
Project description:Neuroendocrine prostate cancer models
| PRJNA449097 | ENA