Recently, increasing evidence indicates a role for cellular prion protein (PrPc) in fostering stemness and invasion of glioblas- toma multiforme (GBM). Besides being implicated in the patho- genesis and transmission of prion diseases, PrPc is emerging as a key in maintaining glioblastoma cancer stem cells (GSCs) phe- notype, thereby strongly affecting GBM infiltration and relapse. This might apply to other proteins, which share a prion-like struc- ture and biology. Thus, suppressing the expression of these pro- teins and occluding their ability to spread from cell-to-cell may be useful to provide novel treatments along with an in-depth knowledge of GBM neurobiology. Since these proteins appear to be regulated by the autophagy pathway, in the present study, we administered the gold standard mTOR inhibitor/autophagy inducer, rapamycin, to analyze the effects on GBM cell cultures concerning the expression of specific prionoids. Rapamycin dose- dependently suppresses the expression of prion-like proteins, while producing a marked differentiation of GBM cells. These effects are remarkable when transwell co-cultures of normal human astrocytes (NHA) are seeded in close contact with GBM cells separated by a semi-permeable membrane. In these experi- mental conditions, a transformation of astrocytes occurs along with increased expression of prionoids, which depends on the spreading of specific molecules through the membrane. Rapamycin administration occludes cell-to-cell spreading, while bringing back NHA to their previous phenotype.

THE EFFECTS OF RAPAMYCIN ON THE OCCURRENCE OF PRIONOIDS IN GLIOBLASTOMA MULTIFORME

Ryskalin L
Primo
;
Gesi M;Ruffoli R;Giorgi F. S;Lenzi P;Fornai. F
Ultimo
2021-01-01

Abstract

Recently, increasing evidence indicates a role for cellular prion protein (PrPc) in fostering stemness and invasion of glioblas- toma multiforme (GBM). Besides being implicated in the patho- genesis and transmission of prion diseases, PrPc is emerging as a key in maintaining glioblastoma cancer stem cells (GSCs) phe- notype, thereby strongly affecting GBM infiltration and relapse. This might apply to other proteins, which share a prion-like struc- ture and biology. Thus, suppressing the expression of these pro- teins and occluding their ability to spread from cell-to-cell may be useful to provide novel treatments along with an in-depth knowledge of GBM neurobiology. Since these proteins appear to be regulated by the autophagy pathway, in the present study, we administered the gold standard mTOR inhibitor/autophagy inducer, rapamycin, to analyze the effects on GBM cell cultures concerning the expression of specific prionoids. Rapamycin dose- dependently suppresses the expression of prion-like proteins, while producing a marked differentiation of GBM cells. These effects are remarkable when transwell co-cultures of normal human astrocytes (NHA) are seeded in close contact with GBM cells separated by a semi-permeable membrane. In these experi- mental conditions, a transformation of astrocytes occurs along with increased expression of prionoids, which depends on the spreading of specific molecules through the membrane. Rapamycin administration occludes cell-to-cell spreading, while bringing back NHA to their previous phenotype.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1116294
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