Signals of Apoptotic Pathways in Several Types of Meningioma

Abstract

Meningiomas are intracranial tumour derived from meningothelial cells, which aggressive behaviour has been frequently associated to cell apoptosis. In this paper activation of several factors involved in apoptosis has been investigated on biopsies of primary, non recurrent meningiomas. Benign (meningotheliomatous, transitional, fibrous, angiomatous), atypical and anaplastic meningiomas were analysed by immunohistochemistry and western blot, to visualize the occurring of different apoptotic pathways and their association with clinical grading. Apoptotic cell have been detected by a double colorimetric staining for TUNEL and caspase-3 active form. Apoptotic signal positive cells have been detected in all type of meningiomas analysed, with exception of meningotheliomatous meningiomas. Differences have been found in the activation of apoptotic pathways between several types of grade I meningiomas and among benign, anaplastic and atypical meningiomas. An intense expression of several apoptotic inhibitor occurred in grade I meningiomas. The correlation among expression of apoptotic and inhibitory factors and cell proliferation index may suggest that in grade I meningiomas apoptosis may be related to mechanisms involved into tumor cells surviving. Instead in grade II and III meningiomas the same correlation seems indicate an high turnover of tumor cells that might be useful as index of cell proliferation and tumor mass growth.

Dysregulation of Apoptosis Caused by Aberrant Histone Modification Influences on the Recurrence of Meningiomas

“…Other factors such as BAX pro-apoptotic protein and BCL2 anti-apoptotic protein complete the biochemical intracellular pathways of apoptotic process [23] that converge on activation of CASP3 [24]. In particular, CASP3 was reported to have a lower expression in WHO grade II and III meningioma than WHO grad I meningioma [33]. In this study, overexpression of survivin and BCL2 and underexpression CASP3 and BAX were associated with high recurrence rate in AMs, which was concordant with previous reports.…”

Epigenetic Role of Histone 3 Lysine Methyltransferase and Demethylase in Regulating Apoptosis Predicting the Recurrence of Atypical Meningioma

“…Other factors such as BAX pro-apoptotic protein and BCL2 anti-apoptotic protein complete the biochemical intracellular pathways of apoptotic process ( 23 ) that converge on activation of CASP3 ( 24 ). In particular, CASP3 was reported to have a lower expression in WHO grade II and III meningioma than WHO grad I meningioma ( 33 ). In this study, overexpression of survivin and BCL2 and underexpression CASP3 and BAX were associated with high recurrence rate in AMs, which was concordant with previous reports.…”

New drug candidates for treatment of atypical meningiomas: An integrated approach using gene expression signatures for drug repurposing

“…Other potential targets for verteporfin include: PARP-1, which is involved in single strand DNA repairs and was recently demonstrated to have highest expression levels in grade II subtypes meningiomas [ 35 ] and the pro-apoptotic protein caspase-3 shown to correlate with the histological grade of meningioma, cell proliferation index and mitotic count [ 36 ]. Furthermore the presence of active Caspase 3 fragments have been demonstrated in atypical meningiomas [ 37 ]. Verteporfin has been shown to induce apoptotic cell death in HeLa cells via induction of caspase 3 [ 38 ], however this mechanism has not been demonstrated in meningioma cells.…”