Similar Datasets
Project description:Tumor macrophages from rejecting and growing tumors
| PRJNA841487 | ENA
Project description:Clinical and experimental evidence indicates that tumor-associated macrophages (TAMs) promote malignant progression. In breast cancer, TAMs enhance tumor angiogenesis, tumor cell invasion, matrix remodeling, and immune suppression against the tumor. In this study, we examined late-stage mammary tumors from a transgenic mouse model of breast cancer. We used flow cytometry under conditions that minimized gene expression changes to isolate a rigorously defined TAM population previously shown to be associated with invasive carcinoma cells. The gene expression signature of this population was compared with a similar population derived from spleens of non-tumor-bearing mice using high-density oligonucleotide arrays. Using stringent selection criteria, transcript abundance of 460 genes was shown to be differentially regulated between the two populations. Bioinformatic analyses of known functions of these genes indicated that formerly ascribed TAM functions, including suppression of immune activation and matrix remodeling, as well as multiple mediators of tumor angiogenesis, were elevated in TAMs. Further bioinformatic analyses confirmed that a pure and valid TAM gene expression signature in mouse tumors could be used to assess expression of TAMs in human breast cancer. The data derived from these more physiologically relevant autochthonous tumors compared with previous studies in tumor xenografts suggest tactics by which TAMs may regulate tumor angiogenesis and thus provide a basis for exploring other transcriptional mediators of TAM trophic functions within the tumor microenvironment. Tumor-associated macrophages from late-stage mouse mammary tumors compared to splenic macrophages from non-tumor-bearing littermate controls. 4 biological replicates of each population were compared via gene expression arrays.
2010-06-21 | E-GEOD-18404 | biostudies-arrayexpress
Project description:Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.
| 2360169 | ecrin-mdr-crc
Project description:Extracellular matrix (ECM) structural and compositional abnormalities are a hallmark of many cancers. Tumor associated macrophages (TAM) are considered pivotal players in mounting pro-tumoral functions; yet, their role in tumor-ECM remodeling remains largely ambiguous. Using an orthotopic murine model of colorectal cancer we defined two major CRC TAM subsets arising from Ly6Chi monocytes recruited in a CCR2-depedent manner. TAM-deficient CRC tumors established Ccr2-/- mice exhibited attenuated growth. Advanced imaging techniques revealed that the enhanced deposition, linearization and cross-linking of collagen fibers typical to tumor growth were absent in the Ccr2-/- tumors. Moreover, the Ccr2-/- tumors displayed altered ECM composition with 348 proteins that were differentially expressed in comparison with WT tumors, among them 46 were ECM related. Integrating transcriptomic and proteomic approaches we defined a TAM signature of ECM remodeling enzymes, structural and affiliated proteins. Specifically, were prominent proteins involved with the synthesis and assembly of collagen type I, IV and XIV. Finally, decellularized 3D ECM fragments extracted from WT tumors, but not from Ccr2-/- tumors or upstream healthy colon, enhanced tumor cell proliferation in vitro and tumor development in the native colonic environment. Collectively, our integrated biophysical-immunologic-omic approaches uncover new mechanistic insights of TAM-mediated remodeling of tumor ECM structure and composition.
2016-09-26 | PXD002094 | Pride
Project description:Tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression. To investigate changes in the phenotype of tumor macrophages following radiation therapy, we FACS sorted tumor macrophages from Panc02 tumors. We have previously shown that we can distinguish mature tumor macrophages from immature myeloid and MDSC populations by expression of Gr1 and IA (MHC class II). To isolate these sub-populations, we first gated CD11b+ cells in the untreated or irradiated tumors, then sorted the CD11b+IA+ macrophage population and the CD11b+Gr1hi MDSC population. Cytospins of the sorted populations demonstrates that the CD11b+Gr1hi MDSC predominantly have a granulocyte morphology and the CD11b+IA+ cells have a macrophage morphology in both the untreated and irradiated tumors. RNA was purified from CD11b+IA+ macrophages from untreated or irradiated tumors 1 day or 7 days following radiation therapy and Gene Expression Microarray analysis was performed. There are untreated and irradiated samples at time points 1 day and 7 days following radiation therapy. The experiment was repeated in entirety, generating a second gene array sample for each. For analysis, the untreated samples of 1 day and 7 days were grouped together.
2011-12-07 | E-GEOD-34206 | biostudies-arrayexpress
Project description:Macrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes. Activation of this transcriptional program correlated with decreased angiogenesis in metastatic tumors and decreased metastatic growth. Comparison of this Ets2-specific TAM expression profile with human breast cancer profiles revealed a macrophage gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung. Breast TAMs were isolated from early-stage PyMT-induced mammary tumors expressing Ets2 and also from the tumors with Ets2-deficient TAMs. Since macrophages have also been implicated in normal mammary gland remodeling, normal remeodeling macrophages were also purified from females expressing Ets2 and the ones where Ets2 is deleted in the macrophages. One RNA sample was extracted from each genetic group for gene-expression profiling.
2010-01-05 | E-GEOD-12863 | biostudies-arrayexpress
Project description:Clinical and experimental evidence indicates that tumor-associated macrophages (TAMs) promote malignant progression. In breast cancer, TAMs enhance tumor angiogenesis, tumor cell invasion, matrix remodeling, and immune suppression against the tumor. In this study, we examined late-stage mammary tumors from a transgenic mouse model of breast cancer. We used flow cytometry under conditions that minimized gene expression changes to isolate a rigorously defined TAM population previously shown to be associated with invasive carcinoma cells. The gene expression signature of this population was compared with a similar population derived from spleens of non-tumor-bearing mice using high-density oligonucleotide arrays. Using stringent selection criteria, transcript abundance of 460 genes was shown to be differentially regulated between the two populations. Bioinformatic analyses of known functions of these genes indicated that formerly ascribed TAM functions, including suppression of immune activation and matrix remodeling, as well as multiple mediators of tumor angiogenesis, were elevated in TAMs. Further bioinformatic analyses confirmed that a pure and valid TAM gene expression signature in mouse tumors could be used to assess expression of TAMs in human breast cancer. The data derived from these more physiologically relevant autochthonous tumors compared with previous studies in tumor xenografts suggest tactics by which TAMs may regulate tumor angiogenesis and thus provide a basis for exploring other transcriptional mediators of TAM trophic functions within the tumor microenvironment.
2009-10-10 | GSE18404 | GEO
Project description:Tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression. To investigate changes in the phenotype of tumor macrophages following radiation therapy, we FACS sorted tumor macrophages from Panc02 tumors. We have previously shown that we can distinguish mature tumor macrophages from immature myeloid and MDSC populations by expression of Gr1 and IA (MHC class II). To isolate these sub-populations, we first gated CD11b+ cells in the untreated or irradiated tumors, then sorted the CD11b+IA+ macrophage population and the CD11b+Gr1hi MDSC population. Cytospins of the sorted populations demonstrates that the CD11b+Gr1hi MDSC predominantly have a granulocyte morphology and the CD11b+IA+ cells have a macrophage morphology in both the untreated and irradiated tumors. RNA was purified from CD11b+IA+ macrophages from untreated or irradiated tumors 1 day or 7 days following radiation therapy and Gene Expression Microarray analysis was performed.
2011-12-07 | GSE34206 | GEO
Project description:Molecular mechanisms of the cancer cells-macrophages interactions growing in vitro conditions as a co-culture. The five canine mammary cancer cell lines were cultured with monocytes sorted from the canine blood for 72hrs. Then, the cancer cells and macrophages were sorted and the gene expression analysis was conducted. The control for each co-cultured cell line was the same cell line growing as a single culture, whereas the control for the macrophages growing in a co-culture conditions were macrophages growing as a single culture. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Dye-swap experiment, each cell line growing in the co-culture conditions was compared to the same cell line growing as a single culture, macrophages growing in the co-culture conditions were compared to the macrophages growing as the single culture.
2012-05-30 | E-GEOD-29339 | biostudies-arrayexpress
Project description:Transcriptional profile of tumor associated macrophages in Ptenpc-/- and Ptenpc-/ Smad4pc-/- tumors
| PRJNA644631 | ENA