Leukemia hijacks a neural mechanism to invade the central nervous system
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471996 | ENA |
REPOSITORIES: ENA
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Project description:Acute lymphoblastic leukemia (ALL) has a striking propensity to metastasize to the central nervous system (CNS).1 In contrast to solid tumor brain metastases, ALL seldom involves the parenchyma but is isolated to the leptomeninges, an infrequent site for carcinomatous invasion.2,3 While CNS metastasis is characteristic across ALL subtypes, a unifying mechanism for invasion has not been determined. Here we show that ALL cells in circulation are unable to breach the blood brain barrier; instead they migrate into the CNS along vessels that passage directly between vertebral or calvarial bone marrow (BM) and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, known to coordinate neuronal progenitor cell pathfinding in the CNS.4-6 The laminin receptor a6 integrin is expressed by most ALL.7,8 We found that a6/laminin mediated ALL migration toward cerebrospinal fluid (CSF) in vitro. ALL-xenografted mice treated with either a PI3Kd inhibitor that decreased ALL a6 expression or specific a6 neutralizing antibodies showed significantly less ALL transit along bridging vessels, CSF blast counts and CNS disease symptoms despite minimally decreased BM disease burden. Our data suggest that a6 integrin expression, common in ALL, allows cells to coopt neural migratory pathways to invade the CNS.
2018-07-12 | GSE114627 | GEO
Project description:Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined. Here we show that ALL cells in the circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor α6 integrin is expressed in most cases of ALL. We found that α6 integrin-laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells, or specific α6 integrin-neutralizing antibodies and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid and CNS disease symptoms despite minimally decreased bone marrow disease burden. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.
| S-EPMC10257142 | biostudies-literature
Project description:Efavirenz Central Nervous System Side Effects
| PRJNA354669 | ENA
Project description:RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases.
PURPOSE: This phase II trial is studying the side effects and how well iodine I 131 monoclonal antibody 3F8 works in treating patients with central nervous system cancer or leptomeningeal cancer.
| 2037925 | ecrin-mdr-crc
Project description:Genomic aberrations in primary central nervous system lymphoma (PCNSL). Two-condition experiment, PCNSLs vs. healthy men. Biological replicates: 12 tumors replicates, 13 peripheral blood replicates.
2010-11-13 | E-GEOD-25298 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25297: Genome-wide gene expression comparison (primary central nervous system lymphoma (PCNSL) vs normal lymph node) GSE25298: Genomic aberrations in primary central nervous system lymphoma (PCNSL) Refer to individual Series
2010-11-13 | E-GEOD-25299 | biostudies-arrayexpress
Project description:Genomic aberrations in primary central nervous system lymphoma (PCNSL).
2010-11-13 | GSE25298 | GEO
Project description:Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a critical determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.
2023-05-17 | PXD041850 | Pride
Project description:The functional outcome of GM-CSF in the central nervous system
| PRJEB27657 | ENA
Project description:Primary central nervous system lymphoma(PCNSL) is a rare extra-nodal non-Hodgkin’s lymphoma and accounts for 3%-4% of central nervous system tumors. Recent studies have highlighted the importance of cerebrospinal fluid derived extracellular vesicles in PCNSL. Extracellular vesicles(EVs) are nanoscale vesicles with bilayer lipid membrane released by almost all cell types. EVs are present in body fluids, including urine, blood and CSF. Cerebrospinal fluid(CSF) is a colorless fluid that surrounds the brain and spinal cord and acts as lymph in the central nervous system. CSF-derived EVs contain proteins from neurons, oligodendrocytes, astrocytes and microglias. Studies of CSF EVs are mainly limited by the amount of EVs isolated from per milliliter of CSF and the volume of CSF acquired from one patient. Here, we provide a label-free quantitative phospho-proteome profiling of EVs separated from PCNSL and non-PCNSL CSF samples by an earlier introduced functional magnetic beads called EVTRAP together with highly sensitive timsTOF Pro.
2023-07-12 | PXD040744 | JPOST Repository