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Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development

ABSTRACT: Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development

PROVIDER: PRJNA604800 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11018030_1.fastq.gz	Fastqsanger.gz
	SRR11018030_2.fastq.gz	Fastqsanger.gz
	SRR11018031_1.fastq.gz	Fastqsanger.gz
	SRR11018031_2.fastq.gz	Fastqsanger.gz
	SRR11018032_1.fastq.gz	Fastqsanger.gz

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Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development

Project description:With a five-year survival rate of 9%, pancreatic ductal adenocarcinoma (PDAC) the deadliest of all cancers. The rapid mortality makes PDAC difficult to research, and inspires a resolve to create reliable, tractable cellular models for preclinical cancer research. PDAC organoids are increasing used to model PDAC as they maintain the differentiation status, molecular and genomic signatures of the original tumour. In this paper, we present novel methodologies and experimental approaches to develop PDAC organoids from PDX tumours, and the simultaneous development of matched primary cell lines. Moreover, we also identify a method of recapitulating primary cell line cultures to organoids (CLOs). We highlight the usefulness of CLOs as PDAC organoid models, as they maintain similar transcriptomic signatures as their matched patient-derived organoids and PDXs. These models provide a manageable, expandable in vitro resource for downstream applications such as high throughput screening, functional genomics, and tumour microenvironment studies.

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Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development.

Project description:With a five-year survival rate of 9%, pancreatic ductal adenocarcinoma (PDAC) is the deadliest of all cancers. The rapid mortality makes PDAC difficult to research, and inspires a resolve to create reliable, tractable cellular models for preclinical cancer research. Organoids are increasingly used to model PDAC as they maintain the differentiation status, molecular and genomic signatures of the original tumour. In this paper, we present novel methodologies and experimental approaches to develop PDAC organoids from PDX tumours, and the simultaneous development of matched primary cell lines. Moreover, we also present a method of recapitulating primary cell line cultures to organoids (CLOs). We highlight the usefulness of CLOs as PDAC organoid models, as they maintain similar transcriptomic signatures as their matched patient-derived organoids and patient derived xenografts (PDX)s. These models provide a manageable, expandable in vitro resource for downstream applications such as high throughput screening, functional genomics, and tumour microenvironment studies.

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Ex vivo modelling of pancreatic cancer recapitulates in vivo extracellular matrix signatures and drug responses

Project description:The ex vivo modelling of pancreatic ductal adenocarcinoma (PDAC) using patient-derived cells is a promising tool to predict treatment responses. Matrigel-based organoid and organotypic approaches are limited by their undefined molecular composition, hindering the recapitulation of the tumour’s characteristic desmoplasia, which is known to promote drug resistance. To overcome these limitations, we used self-assembling peptide amphiphiles (PAs) gelled in a minimal extracellular matrix to model the pancreatic tumour microenvironment and to establish 3D multicellular cultures of patient-derived PDAC cells, pancreatic stellate cells and macrophages. Matrisome analysis of 3D cultures demonstrated consistent ECM protein deposition, which was highly reminiscent of the corresponding primary PDAC tissues. The proteomic data obtained was also compared to the corresponding patient-derived xenografts (PDX) in nude mice and Matrigel-based cultures. Characterisation of the chemosensitivity of the cultures revealed realistic treatment responses by PDAC cells in PA hydrogels based on the responses of their corresponding PDX tumours. Histological, transcriptional and functional techniques confirmed these similarities, which were not observed in Matrigel-based cultures. These findings demonstrate the biomimetic nature of PA hydrogels, which enable cultured cells to recreate the PDAC matrisome ex vivo and to respond to chemotherapeutic agents in a predictive manner.

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Characterizing the Chemoresistant Ovarian Cancer Population using the Heterogeneous PDX

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Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

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