RESUMO
Gliomas display cellular hierarchies with self-renewing tumorigenic glioma stem cells (GSCs) at the apex. The GSC niches function as a regulator of GSC maintenance, however, the exact components of GSC niches that mediate this process are still far from fully defined. Here, we showed that glioma cells with aberrant mesenchymal phenotypes constitute a mesenchymal niche for GSCs. Using patient-derived specimens, we demonstrated that the paracrine PGI signaling, initiated by mesenchymal glioma cells, induces the self-renewal and tumorigenic potentials of GSCs through induction of KLF4. Treatment of intracranial orthotopic xenografts with shPGI or shKLF4 leads to less lethal potency. Our data therefore suggest that blockade of the PGI-KLF4 pathway may provide a therapeutic strategy against GSC niches.
Assuntos
Neoplasias Encefálicas/patologia , Sistema Enzimático do Citocromo P-450/metabolismo , Glioma/patologia , Oxirredutases Intramoleculares/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Mesenquimais/patologia , Células-Tronco Neoplásicas/patologia , Transdução de Sinais , Animais , Western Blotting , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proliferação de Células , Sistema Enzimático do Citocromo P-450/genética , Glioma/genética , Glioma/metabolismo , Humanos , Técnicas Imunoenzimáticas , Oxirredutases Intramoleculares/genética , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
Rosai-Dorfman disease is a well-established autoimmune histioproliferative disorder, and solitary central nervous system involvement is rare. A 35-year-old man presented with headache and transient blurred vision of 4 months' duration and weakness of the left extremities for 1 month. He had left temporal hemianopsia, a right nasal visual field defect of the upper medial quadrant and decreased muscle strength of the left extremities. Magnetic resonance imaging (MRI) showed a contrastenhancing tentorium-based lesion in the right trigone, intruding into the right lateral ventricle. The lesion was totally resected. Rosai-Dorfman disease was confirmed pathologically by an inflammatory infiltrate in the absence of an infectious agent, emperipolesis and positive S100 staining. From a review of the literature on Rosai-Dorfman disease in the central nervous system it is concluded that follow-up MRI should be performed in order to detect possible recurrence and that this rare entity should be considered in the differential diagnosis of intracranial lesions.
