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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumour human scRNA-Seq]

ABSTRACT: Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumour human scRNA-Seq]

PROVIDER: PRJNA983270 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24910185_1.fastq.gz	Fastqsanger.gz
	SRR24910185_2.fastq.gz	Fastqsanger.gz
	SRR24910186_1.fastq.gz	Fastqsanger.gz
	SRR24910186_2.fastq.gz	Fastqsanger.gz
	SRR24910187_1.fastq.gz	Fastqsanger.gz

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumour human scRNA-Seq]

Project description:Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumour cells and the corresponding tumour microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumour epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumour epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Bulk RNA-Seq]

Project description:Peritoneal carcinomatosis (PC) originating from colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Metastasis is the major cause of death in patients with CRC whereas primary locoregionally circumscribed tumors are mostly curable. Due to the lack of appropriate and realistic mouse models for metastasis of CRC until recently, the research about metastasis of these tumors and possible therapeutic options is still in its infancy. With the establishment of murine CRC tumor organoids, mouse models were established which realistically mimic the process of tumor cell metastasis to the liver and the lung. However, to date no appropriate model for PC is described. Here, we establish a realistic model for peritoneal metastasis of colorectal cancer upon surgical transplantation of tumor organoids into the cecum wall. This mouse model for PC recapitulates human PC which makes it an ideal model for research of the biology of metastasis of colorectal cancer to the peritoneal cavity and for its usage for preclinical drug screening as well as for the evaluation of new therapeutic approaches which are highly needed in clinical reality.

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [TIL scRNA-Seq]

Project description:Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumor epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

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Project description:Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumor epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis

Project description:Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis

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Project description:Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Bulk RNA-Seq]

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [TIL scRNA-Seq]

Project description:Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [TIL scRNA-Seq]

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumor scRNA-Seq]

Project description:Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumor scRNA-Seq]

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis

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

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