Gene Expression
Nebulas
Gene Expression NebulasSummary: Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression.
Overall Design: We performed RNA-seq on the human dermal fibroblast cell line DF treated for six hours with PGE-2 or untreated.
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| Growth Protocol: | - |
| Treatment Protocol: | NT; PGE-2 six hours |
| Extract Protocol: | Total RNA was isolated from the cell lines using RNeasy Mini Kit (Qiagen) |
| Library Construction Protocol: | - |
| Molecule Type: | poly(A)+ RNA |
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| Library Layout: | PAIRED |
| Library Strand: | Forward |
| Platform: | ILLUMINA |
| Instrument Model: | Illumina HiSeq 2000 |
| Strand-Specific: | Specific |
| Data Resource | GEN Sample ID | GEN Dataset ID | Project ID | BioProject ID | Sample ID | Sample Name | BioSample ID | Sample Accession | Experiment Accession | Release Date | Submission Date | Update Date | Species | Race | Ethnicity | Age | Age Unit | Gender | Source Name | Tissue | Cell Type | Cell Subtype | Cell Line | Disease | Disease State | Development Stage | Mutation | Phenotype | Case Detail | Control Detail | Growth Protocol | Treatment Protocol | Extract Protocol | Library Construction Protocol | Molecule Type | Library Layout | Strand-Specific | Library Strand | Spike-In | Strategy | Platform | Instrument Model | Cell Number | Reads Number | Gbases | AvgSpotLen1 | AvgSpotLen2 | Uniq Mapping Rate | Multiple Mapping Rate | Coverage Rate |
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