Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 1]

ABSTRACT: We investigated changes to gene expression in 8 murine pancreatic tumour sub-clones response to co-culture with fibroblasts. Tumours are complex ecosystems where phenotypically diverse tumour cells are embedded in a heterocellular environment. Using an in vitro model of intra-tumoral heterogeneity, we show that clonal tumour cell populations establish distinct interactions with stromal fibroblasts to expand phenotypic diversity across tumour and stromal cell populations. Heterocellular interactions drive differential engagement of tumour cell reciprocal signalling pathways, resulting in normalisation of cell-autonomous differences in MAPK signalling but diversification of AKT signalling. Consequently, tumour cell clones display differential cell-autonomous and non-cell autonomous dependencies. These results demonstrate that tumour-stroma interactions amplify tumour cell autonomous diversity and that our existing perspective on tumour cell heterogeneity underestimates functional diversity.

ORGANISM(S): Mus musculus

PROVIDER: GSE135433 | GEO | 2019/09/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 2]

Project description:We investigated changes to murine pancreatic fibroblast gene expression in response to co-culture with 8 murine pancreatic tumour cell sub-populations. Tumours are complex ecosystems where phenotypically diverse tumour cells are embedded in a heterocellular environment. Using an in vitro model of intra-tumoral heterogeneity, we show that clonal tumour cell populations establish distinct interactions with stromal fibroblasts to expand phenotypic diversity across tumour and stromal cell populations. Heterocellular interactions drive differential engagement of tumour cell reciprocal signalling pathways, resulting in normalisation of cell-autonomous differences in MAPK signalling but diversification of AKT signalling. Consequently, tumour cell clones display differential cell-autonomous and non-cell autonomous dependencies. These results demonstrate that tumour-stroma interactions amplify tumour cell autonomous diversity and that our existing perspective on tumour cell heterogeneity underestimates functional diversity.

2019-09-30 | GSE135434 | GEO

Oncogene-dependent regulation of tumor cells via stromal reciprocal signalling

Project description:Cancer is a heterocellular disease composed of tumor cells and stromal cells. Although stromal cells are known to regulate cancer progression, oncogene-dependent signalling through heterocellular cancer systems remains poorly elucidated. Here, we describe KRASG12D-dependent ‘reciprocal’ signalling across tumor and stromal Pancreatic Ductal Adenocarcinoma (PDA) cells. Heterocellular multivariate phosphoproteomics demonstrates how an oncogenic cue (KRASG12D), a trans-cellular signal (SHH), and stromal cells drive a reciprocal response in tumor cells. KRASG12D-dependent reciprocal signalling regulates the tumor cell phosphoproteome, total proteome, and mitochondria activity via an IGFR1/AXL-AKT axis. The reciprocal KRASG12D signalling state requires a heterocellular context and is unreachable by cell-autonomous oncogenic KRAS alone. These findings provide evidence that oncogenic KRAS regulates tumor cells via heterocellular reciprocation. Comparison between FACS resolved iKRAS cells (previously in co-culture with PSCs) pertubed with a SHH antibody

2015-06-27 | E-GEOD-70351 | biostudies-arrayexpress

Oncogene-dependent regulation of tumor cells via stromal reciprocal signalling

2015-06-27 | GSE70351 | GEO

Heterocellular OSM-OSMR signalling drives pancreatic cancer growth and metastasis through functional fibroblast reprogramming

Project description:Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterised by a pathological fibroinflammatory microenvironment. Dichotomous tumour-promoting and -restrictive roles have been ascribed to the tumour microenvironment, however the effects of individual stromal subsets remains incompletely characterised. Here, we describe how heterocellular OSM-OSMR signalling instructs fibroblast reprogramming, tumour growth and metastasis. Macrophage-secreted OSM stimulates inflammatory gene expression in cancer-associated fibroblasts (CAFs), which in turn induce a pro-tumorigenic environment and engage tumour cell survival and migratory signalling pathways. Tumour cells implanted in Osm-deficient (Osm-/-) mice display an epithelial-dominated morphology, reduced tumour growth and did not metastasise. Moreover, the tumour microenvironment of Osm-/- animals exhibit increased abundance of αSMApos myofibroblasts and a shift in myeloid and T cell phenotypes, consistent with a more immunogenic environment. Taken together, these data demonstrate how OSM-OSMR signalling coordinates heterocellular interactions to drive a pro-tumorigenic environment in PDA.

2021-08-30 | GSE161359 | GEO

Heterocellular OSM-OSMR signalling drives pancreatic tumour growth and metastasis through functional fibroblast reprogramming

Project description:Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterised by a pathologicalfibroinflammatorymicroenvironment. Dichotomous tumour-promoting and -restrictive roles have been ascribed to the tumour microenvironment, however thedisparate effect of individual stromal subsets remains incompletely characterised. Here, we describe how heterocellular OSM-OSMR signalling instructsfibroblast reprogramming,tumourgrowth and metastasis.Macrophage-secreted OSM stimulatesinflammatory gene expression in cancer-associated fibroblasts (CAFs), which in turn induce a pro-tumorigenic environment and engage tumour cellsurvival and migratory signalling pathways. Tumour cells implanted in Osm-deficient (Osm-/-) mice display an epithelial-dominated morphology, reduced tumour growth and did notmetastasise. Moreover, the tumour microenvironment of Osm-/-animals exhibit increased abundance of αSMAposmyofibroblasts and a shift in myeloid and T cell phenotypes, consistent with a more immunogenic environment. Taken together, these data demonstrate how OSM-OSMR signalling coordinates heterocellular interactions to drive a pro-tumorigenic environment in PDA.

2021-11-29 | PXD022484 | Pride

Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation

Project description:Oncogenic mutations in tumor cells regulate signaling both within tumor cells and heterotypic stromal cells. However, whether oncogenes regulate tumor cell signaling via stromal cells is poorly understood. Here we show that oncogenic KRAS (KRAS-G12D) uniquely regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with phosphoproteomic multiplexing we conducted a multivariate analysis of heterocellular KRAS-G12D signaling in Pancreatic Ductal Adenocarcinoma (PDA) cells. By engaging heterotypic fibroblasts, KRAS-G12D drives unique reciprocal signaling in tumor cells to employ additional kinases and double the number of regulated signaling nodes from cell-autonomous KRAS-G12D. Heterocellular signaling produces a distinct tumor cell phosphoproteome, total proteome, and increase mitochondria capacity via an IGF1R/AXL-AKT axis. Reciprocal KRAS-G12D phenotypes require a heterocellular context and are unreachable by cell-autonomous KRAS-G12D alone. These results demonstrate oncogene signaling should be viewed as a heterocellular process and our existing homocellular perspective underrepresents the extent of oncogene signaling in cancer.

2016-04-19 | PXD003223 | Pride

Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling

Project description:Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling

| PRJNA558886 | ENA

Project description:Cell-autonomous hepatocyte-specific GP130 signalling

| PRJNA655673 | ENA

Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 2]

Project description:Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 2]

| PRJNA558891 | ENA

Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 1]

Project description:Tumour Cell Heterogeneity Instructs Fibroblast Diversity and Reciprocal Signalling [dataset 1]

| PRJNA558892 | ENA