Evolution of TAM gene expression in ID8 tumors
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PROVIDER: PRJNA521020 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression was analyzed in peritoneal macrophages and TAM from mice injected with ID8 ovarian cancer cells intraperitoneally 5 and 21 days after tumor cell injection. Tumor-associated macrophages (TAM) have been shown to have important roles in the malignant progression of various cancers. However, macrophages also posses intrinsic tumoricidal activity and can promote the activity of cytotoxic lymphocytes, but they rapidly adopt an alternative phenotype within tumors, associated with immune-suppression and trophic functions that support tumor growth. The mechanisms that promote TAM polarization in the tumor-microenvironment remain poorly understood, these mechanisms may represent important therapeutic targets to block the tumor-promoting functions of TAM and restore their anti-tumor potential. Here we have characterized TAM in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and the depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4 mediated reprogramming while inhibiting IFNg-induced gene expression. These studies reveal an unexpected role for tumor-induced membrane-cholesterol efflux in driving the IL-4 signaling and the tumor-promoting functions of TAM, while rendering them refractory to pro-inflammatory stimuli. Thus, preventing cholesterol efflux in TAM could represent a novel therapeutic strategy to block pro-tumor functions and restore anti-tumor immunity.
2019-02-06 | GSE126098 | GEO
Project description:Gene expression was analyzed in peritoneal macrophages and TAM from mice injected with ID8 ovarian cancer cells intraperitoneally 28 days after tumor implantation. Tumor-associated macrophages (TAM) have been shown to have important roles in the malignant progression of various cancers. However, macrophages also posses intrinsic tumoricidal activity and can promote the activity of cytotoxic lymphocytes, but they rapidly adopt an alternative phenotype within tumors, associated with immune-suppression and trophic functions that support tumor growth. The mechanisms that promote TAM polarization in the tumor-microenvironment remain poorly understood, these mechanisms may represent important therapeutic targets to block the tumor-promoting functions of TAM and restore their anti-tumor potential. Here we have characterized TAM in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and the depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4 mediated reprogramming while inhibiting IFNg-induced gene expression. These studies reveal an unexpected role for tumor-induced membrane-cholesterol efflux in driving the IL-4 signaling and the tumor-promoting functions of TAM, while rendering them refractory to pro-inflammatory stimuli. Thus, preventing cholesterol efflux in TAM could represent a novel therapeutic strategy to block pro-tumor functions and restore anti-tumor immunity.
2019-02-05 | GSE126080 | GEO
Project description:Gene expression was analyzed in TAM from mice injected with ID8 ovarian cancer cells intraperitoneally in ABC a1/g1 fl/fl-LysM-Cre mice. Tumor-associated macrophages (TAM) have been shown to have important roles in the malignant progression of various cancers. However, macrophages also posses intrinsic tumoricidal activity and can promote the activity of cytotoxic lymphocytes, but they rapidly adopt an alternative phenotype within tumors, associated with immune-suppression and trophic functions that support tumor growth. The mechanisms that promote TAM polarization in the tumor-microenvironment remain poorly understood, these mechanisms may represent important therapeutic targets to block the tumor-promoting functions of TAM and restore their anti-tumor potential. Here we have characterized TAM in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and the depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4 mediated reprogramming while inhibiting IFNg-induced gene expression. These studies reveal an unexpected role for tumor-induced membrane-cholesterol efflux in driving the IL-4 signaling and the tumor-promoting functions of TAM, while rendering them refractory to pro-inflammatory stimuli. Thus, preventing cholesterol efflux in TAM could represent a novel therapeutic strategy to block pro-tumor functions and restore anti-tumor immunity.
2019-02-05 | GSE126079 | GEO
Project description:The data in this submission relate to whole exome sequencing from murine ovarian cancer cell line ID8. All sequencing was performed by Beckman Coulter Genomics, Grenoble, France in February 2013.
2018-03-31 | E-MTAB-4663 | biostudies-arrayexpress
Project description:The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Targeting breast CSC (BCSC) self-renewal represents an avenue for developing therapeutics; however, the molecular mechanisms that govern self-renewal of BCSCs are poorly understood. Our data show the small molecule ID8 decreases overall cell growth, but increases the self-renewal of Aldefluor+ BCSCs and increases functional metastatic BCSCs in a xenograft model. Microarray analysis showed that ID8 is a pleotropic molecule by increasing numerous pathways, including cytokines and chemokines. However, inhibition of those pathways does not abrogate the ID8-induced increase in Aldefluor+ BCSCs. Rather, ID8 is able to activate MAPK pathway through upregulation of the scaffold protein LAMTOR3 and inhibition of MEK prevented the increase in Aldefluor+ BCSCs. By using ID8 as a molecular tool, we identified a new function of the MAPK pathway in regulating BCSC growth and self-renewal.
2016-11-01 | GSE80213 | GEO
Project description:Ovarian cancer is the leading cause of gynecological cancer related death. The overall 5 year survival rate is only 29%. Over 85% of ovarian cancer patients present with advanced stage III or IV disease characterized by intraperitoneal metastasis when diagnosed. However, the process and mechanism of ovarian tumor metastasis remain poorly understood partially because of the lack of a mouse model which could recapitulate the development of metastatic lesion in an appropriate timeframe. In order to generate a convenient ovarian cancer model with accelerated peritoneal metastasis, we performed an in vivo selection study using ID8 ovarian cancer cells to establish a rapid metastasizing mouse ovarian cancer cell line, designated ID8-M. Syngeneic mice with intraperitoneal inoculation of ID8-M cells showed measurable ascites average 35 days after the inoculation and survived only an average of 52 days, while those inoculated with parental ID8 cells showed measurable ascites after 67 days and survived over 81 days. Further analysis showed that, compared with ID8 tumors, ID8-M tumors resulted in more macrophages in the ascites; and compared to ID8 cells, ID8-M cells were more potent to promote macrophages to acquire a M2 phenotype. A microarray analysis provided information to explain the accelerated metastatic phenotype of ID8-M cells.
2015-03-16 | GSE66934 | GEO
Project description:Sequencing of mRNA from ID8 tumor cells and ID8 tumor cells harvested from ascites of mice 11 weeks after intra peritoneal inoculation show acquisition of cancer stem cell-like features in ascitic tumor cells.
2020-01-06 | E-MTAB-8140 | biostudies-arrayexpress
Project description:We used mouse Clariom-S microarrays to study the gene expression profile of ID8 cancer cells stimulated with C-C Chemokine Ligand 6 (CCL6).
2020-07-05 | GSE153790 | GEO
Project description:Glioblastoma (GBM) is the most common and malignant primary brain tumor. Although immunotherapy has shown promise in certain cancer types, it has not been effective against GBM, largely due to its highly immunosuppressive tumor microenvironment (TMEs), which is rich in tumor-associated macrophages/microglia (TAMs). TAMs in late-stage GBM contribute to T-cell exhaustion and worsen prognosis, but the role of TAMs in earlier stages of tumor development is unclear. By employing genetically engineered mouse models and human samples, we used spatiotemporal single-cell transcriptomics to investigate TAM evolution during GBM progression.
2023-09-06 | GSE241037 | GEO