A synthetic BMP-2 mimicking peptide induces glioblastoma stem cell differentiation.
Biochim Biophys Acta Gen Subj
; 1861(9): 2282-2292, 2017 Sep.
Article
en En
| MEDLINE
| ID: mdl-28687190
ABSTRACT
BACKGROUND:
Glioblastoma (GBM) is the most aggressive type of primary brain tumor, characterized by the intrinsic resistance to chemotherapy due to the presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC differentiation and to sensitize GBM cells to treatments.METHODS:
The BMP-2 mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc chemistry. Structural characterization and prediction of receptor binding were obtained by Circular Dicroism (CD) and NRM analyses. Activation of BMP signalling was evaluated by a luciferase reporter assay and western blot. Pro-differentiating effects of GBMP1a were verified by immunostaining and neurosphere assay in primary glioblastoma cultures.RESULTS:
CD and NMR showed that GBMP1a correctly folds into expected tridimensional structures and predicted its binding to BMPR-IA to the same epitope as in the native complex. Reporter analysis disclosed that GBMP1a is able to activate BMP signalling in GBM cells. Moreover, BMP-signalling activation was specifically dependent on smad1/5/8 phosphorylation. Finally, we confirmed that GBMP1a treatment is sufficient to enhance osteogenic differentiation of Mesenchymal Stem Cells and to induce astroglial differentiation of glioma stem cells (GSCs) in vitro.CONCLUSIONS:
GBMP1a was demonstrated to be a good inducer of GSC differentiation, thus being considered a potential anti-cancer tool to be further developed for GBM treatment. GENERALSIGNIFICANCE:
These data highlight the role of BMP-mimicking peptides as potential anti-cancer agents against GBM and stimulate the further development of GBMP1a-based structures in order to enhance its stability and activity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Fragmentos de Péptidos
/
Células Madre Neoplásicas
/
Glioblastoma
/
Proteína Morfogenética Ósea 2
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Gen Subj
Año:
2017
Tipo del documento:
Article
País de afiliación:
Italia