Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumor-initiating stem cell shapes its microenvironment into an immunosuppressive barrier and pro-tumorigenic niche

ABSTRACT: Tumor-initiating stem cells (TSCs) are critical for drug resistance and immune escape. However, the mutual regulations between TSC and tumor microenvironment (TME) remain unclear. Using DNA-label retaining, single-cell RNA sequencing (scRNA-seq), and other approaches, we investigated intestinal adenoma in response to chemoradiotherapy (CRT), thus identifying therapy-resistant TSCs (TrTSCs). We find bidirectional crosstalk between TSCs and TME using CellPhoneDB analysis. An intriguing finding is that TSCs shape TME into a landscape that favors TSCs for immunosuppression and propagation. Using adenoma-organoid co-cultures, niche-cell depletion, and lineaging tracing, we characterize a functional role of cyclooxygenase-2 (Cox-2)-dependent signaling, predominantly occurring between tumor-associated monocytes and macrophages (TAMMs) and TrTSCs. We show that TAMMs promote TrTSC proliferation through prostaglandin E2 (PGE2)-PTGER4(EP4) signaling, which enhances β-catenin activity via AKT phosphorylation. Thus, our study shows that the bidirectional crosstalk between TrTSC and TME results in a pro-tumorigenic and immunosuppressive contexture.

ORGANISM(S): Mus musculus

PROVIDER: GSE136256 | GEO | 2021/07/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The Lin28b/Wnt5a axis drives pancreas cancer through crosstalk between cancer associated fibroblasts and tumor epithelium

Project description:Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we showed that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrated that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9’s production. Using an orthotopic mouse model of PDAC, we fouind that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stromal. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-‍tumorigenic contexture.

2023-09-19 | PXD045477 |

Single-cell and bulk RNA-seq of human tumor-benign prostate adenocarinoma samples

Project description:Here we performed a detailed characterization of prostate cancer (PCa) tumor endothelial cells (TEC) in order to delineate intercellular crosstalk between TEC and the TME.

2022-06-27 | GSE193337 | GEO

Molecular crosstalk between hepatocytes and hepatic stellate cells.

Project description:Aim of the study was to characterize at a molecular level (changes in transcriptomes) the crosstalk between tumor hepatocytes and activated hepatic stellate cells (HSC) in liver cancer. This was adressed by using a coculture model system of HepaRG cell line (tumor hepatocytes, human), and LX2 cell line (HSC, human). By using genome-wide expression profiling, we demonstrated that hepatocyte-HSC crosstalk is bidirectional and results in the deregulation of functionally relevant gene networks. HepaRG and LX2 cells were cultured alone in serum- and DMSO-free William's E medium or together using 1 M-BM-5m pore size transwell inserts which allow diffusion of media components but prevent cell migration (BD Biosciences, San Jose, CA). Triplicate experiments were performed: HepaRG (culture versus coculture), LX2 (culture versus coculture).

2012-05-31 | E-GEOD-32565 | biostudies-arrayexpress

Molecular crosstalk between hepatocytes and hepatic stellate cells.

2012-06-01 | GSE32565 | GEO

Proteomics analysis of extracellular vesicles from thyroid tumours

Project description:Extracellular vesicles (EVs) participate in cell-stroma crosstalk within tumor microenvironment (TME) and Fb are key elements that contribute to tumor promotion. In thyroid cancer, the most prevalent endocrine malignancy, the relevance of Fb in the TME and EVs is beginning to be deciphered. Using an in vitro model of tumor-stroma crosstalk, we performed the comparative proteomic analysis of EVs secreted in tumoral- and non-tumoral milieu to describe EV-functionality and examine their possible role in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) or non-tumor (NThyOri) thyroid cells were co-cultured with human fibroblasts (Fb). EVs, obtained by ultracentrifugation of conditioned media (CMs), were characterized by mass-spectrometry.

2022-08-02 | PXD028081 | Pride

Transcriptome analysis of pancreatic cancer cells with genetically modified Ptges or Ptger4

Project description:Tumor cell-derived prostaglandin E2 (PGE2) is a tumor cell-intrinsic factor that supports immunosuppression in the tumor microenvironment (TME) by acting on the immune cells, but the impact of PGE2 signaling in tumor cells is unclear. We demonstrate that deleting the PGE2 synthesis enzyme or disrupting autocrine PGE2 signaling through EP4 receptors on tumor cells reverses the T cell-low, myeloid cell-rich TME, activates T cells, and suppresses tumor growth. Mechanistically, Ptges and Ptger4 KO tumor cells exhibited altered T and myeloid cell attractant chemokines, became more susceptible to TNF-a killing, and exhibited reduced adenosine synthesis. Our study reveals an unexpected finding – a non-redundant role for the autocrine mPGES1-PGE2-EP4 signaling axis in pancreatic cancer cells, further nominating mPGES-1 inhibition and EP4 blockade as immune-sensitizing approaches in cancer therapy.

2024-09-21 | GSE275728 | GEO

Spatial Analysis of a Complete DIPG-Infiltrated Brainstem Reveals Novel Ligand-Receptor Mediators of Tumor-to-TME Crosstalk

Project description:Previous studies have highlighted the capacity of brain cancer cells to functionally interact with the tumor microenvironment (TME). This TME-cancer crosstalk crucially contributes to tumor cell invasion and disease progression. In this study, we performed spatial transcriptomic sequencing analysis of a complete annotated DIPG tumor-infiltrated patient brainstem. We identified four distinct tumor subpopulations and assessed respective ligand-receptor pairs that actively promote DIPG tumor progression via crosstalk with endothelial, neuronal and immune cell communities. These interactions might promote DIPG tumor progression and represent novel therapeutic targets.

2024-11-18 | GSE280990 | GEO

Crosstalk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity

Project description:Chimeric antigen receptor (CAR) T cell therapy relies on the activity of a large pool of tumor-targeting cytotoxic effectors. Whether CAR T cells act autonomously or require interactions with the tumor microenvironment (TME) is unclear. Here, we report an essential crosstalk between CAR T cell subsets and the TME for tumor control. Using single-cell RNA sequencing, we revealed profound modification of the TME during CAR T cell therapy. IFN-gamma produced by CAR T cells and host-derived IL-12 not only enhanced endogenous T and NK cell activity but were also essential for sustaining CAR T cell cytotoxicity as revealed by intravital imaging. Compared to CD8+ CAR T cells, CD4+ CAR T cells were more efficient at host immune activation but less capable of tumor killing. In sum, CAR T cells are not acting alone in vivo but rely instead on a cytokine-mediated crosstalk with the TME for optimal activity. Invigorating CAR T cell interplay with the host represents an attractive strategy to prevent relapses.

2021-03-29 | GSE165797 | GEO

Cancer cell-derived ADAM15 dictates macrophage infiltration in colorectal tumors

Project description:Tumor progression and response to treatment is highly affected by interactions between cancer cells and the tumor microenvironment (TME). Many of the soluble factors and signaling receptors involved in this crosstalk are shed by a disintegrin and metalloproteinases (ADAMs). Upregulation of ADAM15 has been linked to worse survival in cancer patients and a tumor-promoting function both in vitro and in murine cancer models. Although ADAM15 has been involved in cell-cell and cell-extracellular matrix interactions, its role in the crosstalk between cancer cells and the TME in vivo remains unexplored. Therefore, we aimed to understand how ADAM15 regulates the cell composition of the TME and how it affects tumor progression. Here, we showed an upregulation of ADAM15 in tumor tissues from rectal cancer patients. Subcutaneous injection of wildtype and ADAM15-knockout CT26 colon cancer cells in syngeneic mice confirmed the pro-tumorigenic role of ADAM15. Profiling of tumors revealed higher immune cell infiltration and cancer cell apoptosis in the ADAM15-deficient tumors. Specifically, loss of ADAM15 led to a reduced number of granulocytes and higher infiltration of antigen-presenting cells, including dendritic cells and macrophages, as well as more T cells. Using in vitro assays, we confirmed the regulatory effect of ADAM15 on macrophage migration and identified ADAM15-derived CYR61 as a potential molecular mediator of this effect. Together, our data suggest that targeting ADAM15 could increase the infiltration of immune cells in colorectal tumors and thereby turn cold tumors hot, resulting in a potentially improved response to combined immunotherapy.

2023-07-24 | PXD041164 | Pride

Transcription profiling of human tumor stem cells (TSC) and their matched glioma cells lines reveals TSCs more closely mirror the phenotype and genotype of primary human tumors than do cancer cell lines

Project description:The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. TSCs derived directly from primary glioblastomas harbor extensive similarities to normal NSC and recapitulate the genotype, gene expression patterns and in vivo biology of human glioblastomas. By contrast, the matched, traditionally grown tumor cell lines do not secondary to in vitro genomic alterations. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors. Analysis of gene expression data is described in Lee et al., Cancer Cell, 2006. Experiment Overall Design: To further understand the differences between NBE- and serum-cultured GBM cells, we generated gene expression profiles of NBE-cells, serum-cells, their derived xenograft tumors, and the original GBMs taken directly from the patients. NBE- and serum-cultured GBM cells from different passages were also included in the analyses in order to evaluate the potential effects of in vitro passage number on gene expression.

2008-06-13 | E-GEOD-4536 | biostudies-arrayexpress

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