ArticleThe Journal of clinical investigation2003
Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
110 citing papers in PubMed, 212 citations in OpenAlex.
- Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial.The Lancet. Oncology · 2012Trial
- Peripheral nerve sheath tumors-on-a-chip: Next-generation platforms for mechanistic and therapeutic studies.Materials today. Advances · 2026Article
- MAPK-dependent release of GDNF from Schwann cells mediates tumor-independent pain in neurofibromatosis 1.Science signaling · 2026Article
- The interaction between oxidative stress and Schwann cells.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Daytime SHP2 inhibitor dosing, when immune cell numbers are elevated, shrinks neurofibromas.Life science alliance · 2025Article
- A haploinsufficiency restoration strategy corrects neurobehavioral deficits in Nf1+/- mice.The Journal of clinical investigation · 2025Article
- Dysregulated mast cell activation induced by diabetic milieu exacerbates the progression of diabetic peripheral neuropathy in mice.Nature communications · 2025Article
- Treatment of Plexiform Neurofibromas : Current Perspectives on Surgery and Medical Treatment.Journal of Korean Neurosurgical Society · 2025Article
- SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma.Molecular neurobiology · 2024Article
- NF1-dependent disruption of the blood-nerve-barrier is improved by blockade of P2RY14.iScience · 2024Article
- C5aR plus MEK inhibition durably targets the tumor milieu and reveals tumor cell phagocytosis.Life science alliance · 2024Article
- TheCancers · 2024Review
- Unbalancing cAMP and Ras/MAPK pathways as a therapeutic strategy for cutaneous neurofibromas.JCI insight · 2024Article
- Interactions between Schwann cell and extracellular matrix in peripheral nerve regeneration.Frontiers in neurology · 2024Review
- Econazole selectively induces cell death in NF1-homozygous mutant tumor cells.Cell reports. Medicine · 2023Article
- Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas.BMC cancer · 2023Review
- Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.Frontiers in oncology · 2023Article
- Multiple Nf1 Schwann cell populations reprogram the plexiform neurofibroma tumor microenvironment.JCI insight · 2022Article
- Current concepts of neurofibromatosis type 1: pathophysiology and treatment.Archives of craniofacial surgery · 2022Article
- Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The NF1 tumor suppressor gene encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras signaling. Mutations in NF1 cause neurofibromatosis type 1 (NF1). The development of neurofibromas, which are complex tumors composed of multiple cell types, is a hallmark of NF1. Somatic inactivation of murine Nf1 in Schwann cells is necessary, but not sufficient, to initiate neurofibroma formation. Neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1+/-) microenvironment. Mast cells infiltrate neurofibromas, where they secrete proteins that can remodel the ECM and initiate angiogenesis. Thus, identification of mechanisms responsible for mast cell migration to tumor microenvironments is important for understanding tumorigenesis and for designing potential therapies. Here, we show that homozygous Nf1 mutant (Nf1-/-) Schwann cells secrete Kit ligand (KitL), which stimulates mast cell migration, and that Nf1+/- mast cells are hypermotile in response to KitL. Furthermore, we link hyperactivation of the Ras-class IA-PI3K-Rac2 pathway to increased Nf1+/- mast cell migration. Thus, these studies identify a novel interaction between Nf1-/- Schwann cells and Nf1+/- mast cells that is likely to be important in neurofibroma formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.