Anghileri E.,Unit of Molecular Neuro oncology |
Eoli M.,Unit of Molecular Neuro oncology |
Paterra R.,Unit of Molecular Neuro oncology |
Ferroli P.,Fondazione IRCCS C. Besta |
And 7 more authors.
Journal of Neuro-Oncology | Year: 2012
Cerebellar liponeurocytoma (cLPN) is a very rare central nervous system (CNS) tumour recently recognized as a clinical and pathological entity distinct from medulloblastoma (MB), and included in the WHO classification of CNS tumours under the heading ''glioneuronal tumours''. cLPN typically develop in adult age and have a favourable prognosis compared with MB. In this work, we reviewed the clinical and neuroradiological data of two novel cases of adult cLPN diagnosed at our institution; one patient developed distant metastases. We tried to identify novel molecular markers for this malignancy. We found that the transcription factor NEUROG1 (but not ATOH1) is expressed in cLPN, unlike normal adult cerebellum, and that fatty acid binding protein 4 (FABP4), typically found in adipocytes, is significantly overexpressed compared with both normal adult cerebellum and human MB. These findings suggest cLPN occur as a result of transformation of cerebellar progenitors, which are distinct from cerebellar granule progenitors, and aberrantly differentiate into adipocyte-like tumour cells. They also suggest that analysis of FABP4 expression is of help to differentiate cLPN from MB. © 2012 Springer Science+Business Media, LLC.
Miranda-Goncalves V.,University of Minho |
Miranda-Goncalves V.,ICVS 3Bs PT Government Associate Laboratory |
Honavar M.,Hospital Pedro Hispano |
Pinheiro C.,University of Minho |
And 11 more authors.
Neuro-Oncology | Year: 2013
Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact ofMCT inhibition in gliomas. Methods. MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) andMCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results.MCT1,MCT4, andCD147were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supportingCHCas anMCT1 inhibitor.Therewas a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions. This is themost comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and antiangiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.© The Author(s) 2012.