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Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumour biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination [DU145-SOX11overexpression_dataset]

ABSTRACT: Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumour biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination [DU145-SOX11overexpression_dataset]

PROVIDER: PRJNA1117040 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29195669_1.fastq.gz	Fastqsanger.gz
	SRR29195669_2.fastq.gz	Fastqsanger.gz
	SRR29195670_1.fastq.gz	Fastqsanger.gz
	SRR29195670_2.fastq.gz	Fastqsanger.gz
	SRR29195671_1.fastq.gz	Fastqsanger.gz

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Study of matrix proteins synthesized by DU145 and PC3 prostate cancer cells alone or in co-culture with prostate-derived fibroblasts.

Project description:Tumor microenvironment or stroma has the potency to regulate the behavior of malignant cells. Fibroblast-like cells are abundant in tumor stroma and they are also responsible for the synthesis of many extracellular matrix components. Fibroblast–cancer cell interplay can modify the functions of both cell types. We applied mass spectrometry and proteomics to unveil the matrisome in 3D spheroids formed by DU145 prostate cancer cells, PC3 prostate cancer cells or prostate derived fibroblasts. Similarly DU145/fibroblast and PC3/fibroblast co-culture spheroids were also analyzed. Western Blotting and immunofluorescence were used to confirm the presence of specific proteins in spheroids. Cancer dissemination was studied by utilizing "out of spheroids" migration and invasion assays. In the spheroid model cancer cell–fibroblast interplay caused remarkable changes in extracellular matrix and accelerated the invasion of DU145 cells. Fibroblasts produced structural matrix proteins, growth factors and matrix metalloproteinases. In cancer cell/fibroblast co-cultures basement membrane components, including laminins (3, 5, 2, 3), heparan sulphate proteoglycan (HSPG2 gene product), and collagen XVIII accumulated in a prominent manner when compared to spheroids that contained fibroblasts or cancer cells only. Furthermore, collagen XVIII was intensively processed to different endostatin isoforms by cancer cell derived cathepsin L. To sum up, fibroblasts can promote carcinoma cell dissemination by several different mechanisms. Extracellular matrix and basement membrane proteins provide attachment sites for cell locomotion promoting adhesion receptors. Growth factors and metalloproteinases are known to accelerate cell invasion. Additionally, cancer cell–fibroblast interplay generates biologically active fragments of basement membrane proteins, such as endostatin.

2020-05-04 | PXD016882 | Pride

Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumour biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination [DU145-SOX11overexpression_dataset]

Project description:Metastatic hormone-naïve prostate cancer (mHNPC) is an infrequent form of this tumour type that is characterized by metastasis at the time of diagnosis and accounts for 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration resistant prostate cancer (mCRPC), the molecular characteristics of mHNPC remain largely unexplored. To characterize the transcriptomic landscape of mHNPC, we generated discovery and validation bulk and single-cell RNA-Seq datasets. We performed integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodelling as a predominant feature of these tumours. Importantly, we discover a central role for the transcription factor SOX11 in triggering a heterotypic communication that is associated to the acquisition of metastatic properties. Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.

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Overexpression of a panel of miRNA mimics in DU145 prostate cancer cells.

Project description:The role of a number of miRNAs found to be differentially expressed in prostate cancer was functionally investigated by overexpressing them in DU145 prostate cancer cells and by analyzing gene expression profiles.

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Effect of FGF19 and TNFalpha on human DU145 prostate cancer cells

Project description:DU145 prostate cancer cells were treated with 50 ng/ml FGF19 and 50 ug/ml heparin, or 10 ng/ml TNFalpha, or both

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Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumour biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination [scRNA-Seq]

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Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumour biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination [Validation dataset]

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Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumour biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination [Discovery dataset]

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Controls and CNTN1 overexpression in DU145 cells and CNTN1 knockdown in DU145 cell-derived prostate cancer stem-like cells

Project description:Prostate cancer stem-like cells were derived from DU145 cells as suspension spheres. DU145 cells were transduced with a CNTN1 over expressing retroviral vector and a control empty vector. DU145 spheres were transduced using a retroviral-based shRNA vector against CNTN1 and a scrambled control shRNA viral vector. Both cell lines were cultured over a couple of passages before RNA was collected.

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Project description:DU145 human prostate cancer cells were injected into the prostate of nude mice and cells metastasizing to lymph node (LN1) grown and experiment repeated to make LN2-4. DU145 human prostate cancer cells were injected into the tail vein of nude mice and cells metastasizing to lung (ivLU1) grown and experiment repeated to make ivLU2-4.

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