P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA658598 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We aimed to evaluated the effect of P-Selectin knockdown in glioblastoma cells on their tumorigenesis and the brain microenvironment. To that end, we have established P-Selectin knockdown GL261 glioblastoma cells by shRNA. For control, scrambled shRNA was used (NC). P-Selectin kncockdown and NC GL261 cells were inoculated intra-cranially into mice. 16-21 days post tumor cell inoculation, cancer cells and cells of the tumor microenvironment were isolated using magnetic beads cell separation. We showed meaningful changes in gene expression and cluster distributions between the groups.
2021-02-22 | GSE156663 | GEO
Project description:Glioblastoma (GB) is a highly invasive type of brain cancer exhibiting poor prognosis. As such, its microenvironment plays a crucial role in its progression. Among the brain stromal cells, the microglia were shown to facilitate GB invasion and immunosuppression. However, the reciprocal mechanisms by which GB cells alter microglia/macrophages behavior are not fully understood. We propose that these mechanisms involve adhesion molecules such as the Selectins family. These proteins are involved in immune modulation and cancer immunity. We show that P-selectin mediates microglia-enhanced GB proliferation and invasion by altering microglia/macrophages activation state. We demonstrate these findings by pharmacological and molecular inhibition of P-selectin which leads to reduced tumor growth and increased survival in GB mouse models. Our work sheds light on tumor-associated microglia/macrophage function and the mechanisms by which GB cells suppress the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy.
| S-EPMC7997963 | biostudies-literature
Project description:We used microarrays to detail the global gene expression in peritoneal macrophages (PM) from E-selectin+/+ and E-selectin-/- mouse infected with Listeria Monocytogenes in vivo on day3
2018-01-25 | GSE90808 | GEO
Project description:Tumor cell extravasation takes place, similar to leukocytes, in a multi-step process by which cells emigrate from the blood stream through the vascular endothelium into the tissue. Selectins are regarded as the most important molecules for the first capturing step of the cascade. Whether all tumor cells employ selectin dependent adhesion to metastasize or there is an alternative mechanism still is an open question. Comparative transcriptomic analysis of OVCAR8 and SKOV3 cultured cells and revealed that one third of genes encoding proteins involved in the selectin dependent leukocyte like adhesion cascade show lower expression levels in OVCAR8 cultured cells in comparison to that in SKOV3 cultured cells. In contrast to SKOV3 cells, c-Fos overexpression in OVCAR8 cells does not significantly influence expression of the leukocyte like adhesion cascade genes leaving them at similar levels as in control OVCAR8 cells. The intraperitoneal xenograft model of OVCAR8 cells demonstrated that aggressiveness of OVCAR8-derived tumors is not dependent of c-Fos expression level and comparable with that for SKOV3 control tumors. Based on transcriptome array data we analyzed in details expression of genes encoding proteins involved in the leukocyte like adhesion cascade, E- and P-selectin ligands, as well as glycosylation enzymes in both type of tumors. Our results suggest that selectin-dependent mechanism is not the only for adhesion of OVCAR8 ovarian cancer cells. There is at least one additional mechanism of extravasation that does not rely on selectins.
2017-03-31 | GSE97226 | GEO
Project description:For patients with chronic limb-threatening ischemia and limited revascularization options, alternate means for therapeutic angiogenesis and limb salvage are needed. E-selectin is a cell adhesion molecule that is critical for inflammation and neovascularization in areas of wound healing and ischemia. Here, we tested the efficacy of modifying ischemic limb tissue by intramuscular administration of E-selectin/AAV2/2 (adeno-associated virus serotype 2/2) to modulate angiogenic and inflammatory responses in a murine hindlimb gangrene model. Limb appearance, reperfusion, and functional recovery were assessed for 3 weeks after induction of ischemia. Mice receiving E-selectin/AAV2/2 gene therapy had reduced gangrene severity, increased limb and footpad perfusion, enhanced recruitment of endothelial progenitor cells, and improved performance on treadmill testing compared to control group. Histologically, E-selectin/AAV2/2 gene therapy was associated with increased vascularity and preserved myofiber integrity. E-selectin/AAV2/2 gene therapy also upregulated a panel of pro-angiogenic genes yet downregulated another group of genes associated with the inflammatory response. This novel gene therapy did not induce adverse effects on coagulability, or hematologic, hepatic, and renal function. Our findings highlight the potential of E-selectin/AAV2/2 gene therapy for improving limb perfusion and function in patients with chronic limb-threatening ischemia.
2022-04-29 | GSE201476 | GEO
Project description:For patients with chronic limb-threatening ischemia and limited revascularization options, alternate means for therapeutic angiogenesis and limb salvage are needed. E-selectin is a cell adhesion molecule that is critical for inflammation and neovascularization in areas of wound healing and ischemia. Here, we tested the efficacy of modifying ischemic limb tissue by intramuscular administration of E-selectin/AAV2/2 (adeno-associated virus serotype 2/2) to modulate angiogenic and inflammatory responses in a murine hindlimb gangrene model. Limb appearance, reperfusion, and functional recovery were assessed for 3 weeks after induction of ischemia. Mice receiving E-selectin/AAV2/2 gene therapy had reduced gangrene severity, increased limb and footpad perfusion, enhanced recruitment of endothelial progenitor cells, and improved performance on treadmill testing compared to control group. Histologically, E-selectin/AAV2/2 gene therapy was associated with increased vascularity and preserved myofiber integrity. E-selectin/AAV2/2 gene therapy also upregulated a panel of pro-angiogenic genes yet downregulated another group of genes associated with the inflammatory response. This novel gene therapy did not induce adverse effects on coagulability, or hematologic, hepatic, and renal function. Our findings highlight the potential of E-selectin/AAV2/2 gene therapy for improving limb perfusion and function in patients with chronic limb-threatening ischemia.
2022-04-29 | GSE201479 | GEO
Project description:The 18 kDa translocator protein (TSPO) emerges as an important PET biomarker to assess the tumor microenvironment (TME) in glioblastoma. However, various cellular sources hamper interpretation and biological understanding of TSPO and other immune biomarkers in the TME. Thus, we established a novel method, combining immunomagnetic cell sorting after radiotracer injection (scRadiotracing) with 3D histology via light sheet microscopy and proteomics to dissect cellular allocation of TSPO enrichment in glioblastoma. Single tumor cells of implanted SB28 glioblastoma mice indicated 1.37-fold higher TSPO tracer uptake and 1.46-fold higher TSPO protein expression levels when compared to tumor associated microglia/macrophages (TAMs). Using proteomics, we compared the proteome of tumor associated microglia/macrophages (TAMs), Tumor tissue (TT) and control microglia from WT mice without glioblastoma. This analysis identified TAM specific targets for PET radioligand development with additional potential to monitor diverse TAM subpopulations in vivo. In summary, our data indicate that tumor cells need to be acknowledged as the main contributor to TSPO as a biomarker in glioblastoma. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of complex PET signal sources and will serve to validate novel TAM specific radioligands.
2023-10-30 | PXD044033 | Pride
Project description:E-selectin binding induces transcriptome changes in breast cancer cells to promote bone metastasis
2019-02-22 | GSE96754 | GEO
Project description:Studies of adult human hematopoiesis have until now relied on the expression of CD10 to define lymphoid commitment. We report a novel lymphoid-primed population in human bone marrow that is generated from hematopoietic stem cells (HSC) prior to the onset of CD10 expression and B cell commitment, and is identified by high levels of the homing molecule L-selectin (CD62L). CD10-CD62Lhi progenitors have full lymphoid (B/T/NK) potential, and show reduced myeloid and absent erythroid potential. Genome-wide gene expression analysis demonstrates that the CD10-CD62Lhi population represents an intermediate stage of differentiation between CD34+CD38- HSC and CD34+lin-CD10+ progenitors marked by down-regulation of TAL1 and MPL, upregulation of E2A, CD3E and IL2RG expression, and absent B cell commitment or RAG1/2 expression. Immature CD34+CD1a- thymocytes are also CD62Lhi and L-selectin ligands are expressed at the cortico-medullary junction, suggesting a possible role for L-selectin in human thymic homing. These studies identify the earliest stage of lymphoid priming in human bone marrow. Freshly harvested human bone marrow was ficoll purified, enriched for CD34+, and then FACS sorted. It was then sorted into 3 samples CD34+CD38-, CD34+ CD10- CD62L++, and CD34+ CD10+, with 3 independent biological replicates
2012-08-14 | E-GEOD-35685 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy. Resident microglia and invading macrophages have been shown to have distinct origin and function. Whereas yolk sac-derived microglia reside in the brain, blood-derived monocytes invade the central nervous system only under pathological conditions like tumor formation. We recently showed that disruption of the SIRP?-CD47 signaling axis is efficacious against various brain tumors including GBM primarily by inducing tumor phagocytosis. However, most effects are attributed to macrophages recruited from the periphery but the role of the brain resident microglia is unknown. Here, we sought to utilize a model to distinguish resident microglia and peripheral macrophages within the GBM-TAM pool, using orthotopically xenografted, immunodeficient, and syngeneic mouse models with genetically color-coded macrophages (Ccr2 RFP) and microglia (Cx3cr1 GFP). We show that even in the absence of phagocytizing macrophages (Ccr2 RFP/RFP), microglia are effector cells of tumor cell phagocytosis in response to anti-CD47 blockade. Additionally, macrophages and microglia show distinct morphological and transcriptional changes. Importantly, the transcriptional profile of microglia shows less of an inflammatory response which makes them a promising target for clinical applications.
| S-EPMC6338872 | biostudies-literature