Unique pattern of neutrophil migration and function during tumor progression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA485345 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancers exhibited much more spontaneous migration to tissues. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and much more production of ATP. Their enhanced spontaneous migration was mediated by the binding of ATP to purinergic receptors. In ectopic tumor models and the late stages of cancers, bone marrow neutrophils demonstrated potent immunosuppressive activity. However, these cells had metabolic and migratory activity indistinguishable from that of control neutrophils. A similar pattern of migration was observed in neutrophils and polymorphonuclear myeloid-derived suppressor cells from patients with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer and demonstrate the mechanism of neutrophils’ contribution to early tumor dissemination.
2018-09-27 | GSE118366 | GEO
Project description:miRNA overexpression modulates neutrophil migration
| PRJNA704949 | ENA
Project description: Not available
| S-EPMC6195445 | biostudies-literature
Project description:miR-99 overexpression modulates neutrophil migration
| PRJNA605187 | ENA
Project description:RORa is required for neutrophil migration
| PRJNA719817 | ENA
Project description:Tumor-associated neutrophils are found in many types of cancer and are often reported to contribute to negative outcomes. Several studies have shown that the presence of TGF-β in the tumor microenvironment contributes to the skewing of neutrophils to have a more pro-tumor phenotype. However, the direct effects of TGF-β on neutrophil signaling and migration are unclear. We sought to characterize TGF-β signaling in both primary human neutrophils and the neutrophil-like cell line HL-60 and determine whether TGF-β directly induces neutrophil migration. We found that TGF-β1 does not induce neutrophil migration in either a transwell or an underagarose migration assay. However, TGF-β1 does activate signals canonically through SMAD3 and noncanonically through ERK1/2 in neutrophils in a time and dose-dependent manner. Additionally, TGF-β1 present in the tumor-conditioned media (TCM) is responsible for SMAD3 activation. Moreover, we discovered that TCM from aggressive breast cancer cells induces neutrophils to secrete leukotriene B4 (LTB4), which is a lipid mediator important for amplifying neutrophil recruitment. However, we found that TGF-β1 alone does not induce secretion of LTB4. We next performed RNA-sequencing to evaluate the effects of TGF-β1 and TCM on the neutrophil transcriptome. We found that TGF-β1 and TCM result in changes in gene transcription in HL-60 cells, specifically of two pro-tumor genes OSM and VEGFA. Together, our findings characterize the effects of TGF-β1 on neutrophil signaling, migration, and gene expression that can be applied to understanding the changes in neutrophils that occur in the tumor microenvironment.
2023-08-10 | GSE230490 | GEO
Project description:Pathologically activated neutrophils (PMN) with immune suppressive activity - myeloid-derived suppressor cells (PMN-MDSC) - play a critical role in regulation of tumor progression. They were implicated in promotion of tumor metastases by contributing to pre-metastatic niche formation. This effect was facilitated by enhanced spontaneous migration of PMN in early stage cancers. The molecular mechanisms underpinning this phenomenon remained unclear. We found that syntaphilin (SNPH), a cytoskeletal protein previously known for anchoring mitochondria to the microtubule in neurons and tumor cells, could regulate migration of PMN. Expression of SNPH was decreased in PMN from tumor bearing mice and cancer patients as compared to PMN from tumor-free mice and healthy donors, respectively. Deletion of SNPH increased spontaneous migration of PMN and promoted tumor metastasis. Mechanistically, deletion of SNPH increased the speed and distance travelled by mitochondria, elevated rates of oxidative phosphorylation and glycolysis, and increased generation of adenosine. Thus, our study reveals a molecular mechanism regulating increased migratory activity of PMN during cancer progression and suggests novel targeting opportunity.
2022-12-06 | GSE190505 | GEO
Project description:The miR-199-CDK2 axis modulates neutrophil migration and systemic inflammation
| PRJNA524286 | ENA
Project description:Background. Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. Their nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through constricted space, where the nuclear shape must change in order to fit through. This happens many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Results. Total RNA-sequencing identified that neutrophil migration through 5 or 14 µm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes, when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeleton remodelling. Hi-C was used to capture the genome organisation in control and migrated cells. Chromatin did not switch between the active (A) and inactive (B) compartments after migration. However, global depletion of mid- to long-range contacts was observed following active migration through the 5 µm pores. Chromatin contacts that decreased in frequency were enriched in inactive chromatin. Conclusion. Mid- to long-range contacts are preferentially lost within inactive chromatin, thus protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in human health and disease.
2018-10-04 | GSE115632 | GEO
Project description:Background. Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. Their nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through constricted space, where the nuclear shape must change in order to fit through. This happens many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Results. Total RNA-sequencing identified that neutrophil migration through 5 or 14 µm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes, when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeleton remodelling. Hi-C was used to capture the genome organisation in control and migrated cells. Chromatin did not switch between the active (A) and inactive (B) compartments after migration. However, global depletion of mid- to long-range contacts was observed following active migration through the 5 µm pores. Chromatin contacts that decreased in frequency were enriched in inactive chromatin. Conclusion. Mid- to long-range contacts are preferentially lost within inactive chromatin, thus protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in human health and disease.
2018-08-14 | GSE115633 | GEO