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Cancer associated fibroblasts play an important role in prostate cancer progression

ABSTRACT: Cancer associated fibroblasts play an important role in prostate cancer progression

PROVIDER: PRJNA882042 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21627112_1.fastq.gz	Fastqsanger.gz
	SRR21627112_2.fastq.gz	Fastqsanger.gz
	SRR21627113_1.fastq.gz	Fastqsanger.gz
	SRR21627113_2.fastq.gz	Fastqsanger.gz
	SRR21627114_1.fastq.gz	Fastqsanger.gz

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Cancer associated fibroblasts play an important role in prostate cancer progression [RNA-Seq]

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Cancer associated fibroblasts play an important role in prostate cancer progression [ChIP-Seq]

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Cancer associated fibroblasts play an important role in prostate cancer progression [ATAC-Seq]

Project description:To understand the cell types changes in prostate cancer progression, we carried out scRNA-seq of prostates from different kinds of genetic mouse model. After that, we found fibroblasts were changed obviously during prostate cancer progression. To confirm the function of the fibroblasts, LNCap was used to cocultured with all kinds of fibroblasts in control or ADT condition. To find out the key enviroment factors induced firoblast changing, RNA-seq, ATAC-seq and ChIP-seq of fibroblast in different treatment were taken. And finally, ADT, TGF-β1, and sox4 were confirmed as contributors of the stroma cell changes, which provided new strategies for prostate cancer treatment. scRNA-seq were used to find out the cell lines diverisity of prostate cancer progressiom. RNA-seq of LNCap cocultured with different fibroblasts were taken to identify the pathway fibroblasts induced. RNA-seq, ATAC-seq and ChIP-seq of fibroblasts were carried out to find out the reason of fibroblast changes.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Ratiometric Inclusion of Fibroblasts Promotes Both Castration-resistant and Androgen-dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues

Project description:To investigate the ratiometric role of fibroblasts in prostate cancer (PCa) progression, this work establishes a matrix-inclusive, three-dimensional engineered prostate cancer tissue (EPCaT) model that enables direct coculture of neuroendocrine-variant castration-resistant (CPRC-ne) or androgen-dependent (ADPC) PCa cells with tumor-supporting stromal cell types. Results show that the inclusion of fibroblasts within CRPC-ne and ADPC EPCaTs drives PCa aggression through significant matrix remodeling and increased proliferative cell populations. Interestingly, this is observed to a much greater degree in EPCaTs formed with a small number of fibroblasts relative to the number of PCa cells. Fibroblast coculture also results in ADPC behavior more similar to the aggressive CRPC-ne condition, suggesting fibroblasts play a role in elevating PCa disease state and may contribute to the ADPC to CRPC-ne switch. Bulk transcriptomic analyses additionally elucidate fibroblast-driven enrichment of hallmark gene sets associated with tumorigenic progression. Finally, the EPCaT model clinical relevancy is probed through a comparison to the Cancer Genome Atlas (TCGA) PCa patient cohort; notably, similar gene set enrichment is observed between EPCaT models and the patient primary tumor transcriptome. Taken together, study results demonstrate the potential of the EPCaT model to serve as a PCa-mimetic tool in future therapeutic development efforts.

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