1. Specific Preferences in Lineage Choice and Phenotypic Plasticity of Glioma Stem Cells Under BMP4 and Noggin Influence.
- Author
-
Videla Richardson GA, Garcia CP, Roisman A, Slavutsky I, Fernandez Espinosa DD, Romorini L, Miriuka SG, Arakaki N, Martinetto H, Scassa ME, and Sevlever GE
- Subjects
- Aged, Antigens, CD metabolism, Bone Morphogenetic Protein 4 pharmacology, Carrier Proteins pharmacology, Cell Differentiation drug effects, Cell Differentiation genetics, Female, Gene Expression Regulation, Neoplastic genetics, Humans, Intercellular Signaling Peptides and Proteins pharmacology, Male, Middle Aged, Nerve Tissue Proteins metabolism, Phenotype, Signal Transduction drug effects, Signal Transduction physiology, Tumor Cells, Cultured pathology, Tumor Cells, Cultured physiology, Bone Morphogenetic Protein 4 metabolism, Brain Neoplasms pathology, Carrier Proteins metabolism, Glioma pathology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology
- Abstract
Although BMP4-induced differentiation of glioma stem cells (GSCs) is well recognized, details of the cellular responses triggered by this morphogen are still poorly defined. In this study, we established several GSC-enriched cell lines (GSC-ECLs) from high-grade gliomas. The expansion of these cells as adherent monolayers, and not as floating neurospheres, enabled a thorough study of the phenotypic changes that occurred during their differentiation. Herein, we evaluated GSC-ECLs' behavior toward differentiating conditions by depriving them of growth factors and/or by adding BMP4 at different concentrations. After analyzing cellular morphology, proliferation and lineage marker expression, we determined that GSC-ECLs have distinct preferences in lineage choice, where some of them showed an astrocyte fate commitment and others a neuronal one. We found that this election seems to be dictated by the expression pattern of BMP signaling components present in each GSC-ECL. Additionally, treatment of GSC-ECLs with the BMP antagonist, Noggin, also led to evident phenotypic changes. Interestingly, under certain conditions, some GSC-ECLs adopted an unexpected smooth muscle-like phenotype. As a whole, our findings illustrate the wide differentiation potential of GSCs, highlighting their molecular complexity and paving a way to facilitate personalized differentiating therapies., (© 2015 International Society of Neuropathology.)
- Published
- 2016
- Full Text
- View/download PDF