Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE220506 | GEO | 2024/01/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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.

2024-01-10 | GSE220175 | GEO

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.

2024-01-10 | GSE234804 | GEO

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.

2022-06-27 | GSE202454 | GEO

Peritoneal Carcinomatosis of gastric cancer

Project description:Peritoneal carcinomatosis is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. A major mechanism in peritoneal carcinomatosis is the dissemination of cancer cells into the abdominal cavity, mainly in diffuse gastric adenocarcinoma. The features that enable diffuse primary gastric tumours to develop peritoneal dissemination have been little investigated and are only incompletely understood. We therefore compared the gene expression profile in patients with diffuse primary gastric cancer with and without peritoneal carcinomatosis. Specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Keywords: Disease state analysis

2008-01-31 | GSE8657 | GEO

HAPLN1 potentiates peritoneal metastasis in pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favored a more permissive microenvironment, which accelerated the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promoted TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modified cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identified HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.

2023-03-31 | GSE211126 | GEO

Gene expression analysis of HER2+ breast leptomeningeal carcinomatosis

Project description:Patient-derived primary HER2+ Leptomeningeal carcinomatosis (Lepto) cell lines were established. RNA-seq in various breast cancer cell lines were conducted to characterize the established cell lines. Gene expression analysis clearly indicated thatt Lepto cell lines are transcriptionally different from HER2 positive and negative metastatic breast cancer cell lines such as BT474 and MDA-MB-231 cells.

2021-07-05 | GSE179280 | GEO

Cytokine profile of ascites derived from patients with peritoneal carcinomatosis

Project description:Cytokine profile of ascites derived from patients with peritoneal carcinomatosis

| PRJNA781843 | ENA

Expression data of ascites treated peritoneal carcinomatosis human cell lines

Project description:Expression data of ascites treated peritoneal carcinomatosis human cell lines

| PRJNA781132 | ENA

Expression data of peritoneal carcinomatosis human cell lines co-treated with patient derived ascites and ligand inhibitor

Project description:Characterizations of ascites proteome from ovarian peritoneal carcinomatosis (PC) and gastric PC have demonstrated that ascites contains elevated pro-tumorigenic factors. Reasoning that the composition of ascitic fluid might offer insight into the memory of key biological events occurring intra-abdominally, we hypothesized that paracrine factors essential for survival and growth of peritoneal deposits are secreted into and circulate within ascitic fluid. Our data from cytokine array profile suggest that ascites contains biologically active ligands capable of supporting cellular functions of cancer cells. To decipher downstream signalling pathways activated in cancer cells when exposed to ascites, we performed gene expression analysis of Colo-205 cells upon exposure to PC ascites and ligand inhibitor.

2022-02-22 | GSE189137 | GEO

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

| PRJNA836138 | ENA