PloS one, 2011-09, Vol.6 (9), p.e25222-e25222
2011
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- Autor(en) / Beteiligte
- Titel
- Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12
- Ist Teil von
- PloS one, 2011-09, Vol.6 (9), p.e25222-e25222
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Glioblastoma multiforme (GBM) is the most common and malignant form of glioma with high mortality and no cure. Many human cancers maintain a complex inflammatory program triggering rapid recruitment of inflammatory cells, including mast cells (MCs), to the tumor site. However, the potential contribution of MCs in glioma has not been addressed previously. Here we report for the first time that MCs infiltrate KRas+Akt-induced gliomas, using the RCAS/TV-a system, where KRas and Akt are transduced by RCAS into the brains of neonatal Gtv-a- or Ntv-a transgenic mice lacking Ink4a or Arf. The most abundant MC infiltration was observed in high-grade gliomas of Arf-/- mice. MC accumulation could be localized to the vicinity of glioma-associated vessels but also within the tumor mass. Importantly, proliferating MCs were detected, suggesting that the MC accumulation was caused by local expansion of the MC population. In line with these findings, strong expression of stem cell factor (SCF), i.e. the main MC growth factor, was detected, in particular around tumor blood vessels. Further, glioma cells expressed the MC chemotaxin CXCL12 and MCs expressed the corresponding receptor, i.e. CXCR4, suggesting that MCs could be attracted to the tumor through the CXCL12/CXCR4 axis. Supporting a role for MCs in glioma, strong MC infiltration was detected in human glioma, where GBMs contained significantly higher MC numbers than grade II tumors did. Moreover, human GBMs were positive for CXCL12 and the infiltrating MCs were positive for CXCR4. In conclusion, we provide the first evidence for a role for MCs in glioma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0025222Titel-ID: cdi_plos_journals_1308504033
- Format
- –
- Schlagworte
- Accumulation, Adult, Aged, AKT protein, Anatomy & physiology, Angiogenesis, Animals, Biochemistry, Biology, Blood vessels, Blotting, Western, Brain cancer, Brain Neoplasms - immunology, Brain Neoplasms - metabolism, Brain Neoplasms - pathology, Brain tumors, Cells, Cultured, Chemokine CXCL12 - metabolism, Chemokines, CXCL12 protein, CXCR4 protein, Cyclin-Dependent Kinase Inhibitor p16 - physiology, Cyclin-dependent kinase inhibitors, Dermatologi och venerologi, klinisk genetik, invärtesmedicin, Dermatology and venerology,clinical genetics, internal medicine, Female, Fibroblasts, Fluorescent Antibody Technique, Genetic engineering, Glioblastoma, Glioblastoma - immunology, Glioblastoma - metabolism, Glioblastoma - pathology, Glioblastoma multiforme, Glioblastomas, Glioma, Glioma cells, Growth factors, Health aspects, Humans, Immunoenzyme Techniques, Immunology, Infections, Infiltration, Inflammation, INK4 protein, Internal medicine, Invärtesmedicin, K-Ras protein, Laboratories, Male, Mast cells, Mast Cells - metabolism, Mast Cells - pathology, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Medical prognosis, MEDICIN, MEDICINE, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Metastases, Mice, Mice, Knockout, Middle Aged, Molecular medicine (genetics and pathology), Molekylär medicin (genetik och patologi), Neonates, Neovascularization, Nervous system, Neurobiology, Neurosciences, Pathology, Physiology, Proto-Oncogene Proteins c-akt - metabolism, Proto-Oncogene Proteins p21(ras) - metabolism, Receptors, CXCR4 - metabolism, Recruitment, Rodents, Stem cell factor, Stem Cell Factor - metabolism, Stem cells, Studies, Transgenic animals, Transgenic mice, Tumorigenesis, Tumors