Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq of human ex vivo ovarian cancer models - part III

ABSTRACT: Ascites or solid tumour samples from patients with ovarian cancer were collected and grown in culture as ex vivo models of purified tumour cells. RNA-seq was performed on these models to establish gene expression profiles, which allow identification of genes that are differentially expressed between patients with differing tumour intrinsic properties. These samples have been interrogated for the presence of a gene expression signature indicative of sensitivity to an inhibitor of poly(ADP-ribose) glycohydrolase (PARG). These samples are processed in the same manner as previous studies: “E-MTAB-7223 - RNA-seq of human ex vivo ovarian cancer models with matched stromal cells” and “E-MTAB-10801 - RNA-seq of human ex vivo ovarian cancer models with matched stromal cells - part II” with no stromal counterparts included in this current sequencing batch.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: I-Hsuan Lin

PROVIDER: E-MTAB-11000 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Background: Transcoelomic spread is the major route of metastasis of ovarian high-grade serous carcinoma (HGSC) with the omentum as the major metastatic site. Its unique tumor microenvironment with its large populations of adipocytes, mesothelial cells and immune cells establishes an intercellular signaling network that is instrumental for metastatic growth yet poorly understood. Methods: Based on transcriptomic analysis of tumor cells, tumor-associated immune and stroma cells we defined intercellular signaling pathways for 284 cytokines and growth factors and their cognate receptors after bioinformatic adjustment for contaminating cell types. The significance of individual components of this network was validated by analyzing clinical correlations and potentially pro-metastatic functions, including tumor cell migration, pro-inflammatory signal transduction and TAM expansion. Results: The data show an unexpected prominent role of host cells, and in particular of omental adipocytes, mesothelial cells and fibroblasts (CAF), in sustaining this signaling network. These cells, rather than tumor cells, are the major source of most cytokines and growth factors in the omental microenvironment (n=176 versus n=13). Many of these factors target tumor cells, are linked to metastasis and are associated with a short survival. Likewise, tumor stroma cells play a major role in both extracellular-matrix-triggered and lipid-mediated signaling. We have verified the functional significance of our observations for three exemplary instances. We show that the omental microenvironment (i) stimulates tumor cell migration via WNT4 which is highly expressed by CAF; (ii) induces pro-tumorigenic TAM proliferation in conjunction with high CSF1 expression by omental stroma cells and (iii) triggers pro-inflammatory signaling, at least in part via a HSP70 – NFkB pathway. Conclusions: The intercellular signaling network of omental metastases is majorly dependent on factors secreted by immune and stroma cells to provide an environment that supports ovarian HGSC progression. Clinically relevant pathways within this network represent novel options for therapeutic intervention.

Dataset Information

RNA-seq of human ex vivo ovarian cancer models - part III

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets