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Extracellular vesicles in the biology of brain tumour stem cells--Implications for inter-cellular communication, therapy and biomarker development.
Semin Cell Dev Biol 2015; 40:17-26SC

Abstract

Extracellular vesicles (EVs) act as carriers of molecular and oncogenic signatures present in subsets of tumour cells and tumour-associated stroma, and as mediators of intercellular communication. These processes likely involve cancer stem cells (CSCs). EVs represent a unique pathway of cellular export and cell-to-cell transfer of insoluble molecular regulators such as membrane receptors, signalling proteins and metabolites, thereby influencing the functional integration of cancer cell populations. While mechanisms that control biogenesis, cargo and uptake of different classes of EVs (exosomes, microvesicles, ectosomes, large oncosomes) are poorly understood, they likely remain under the influence of stress-responses, microenvironment and oncogenic processes that define the biology and heterogeneity of human cancers. In glioblastoma (GBM), recent molecular profiling approaches distinguished several disease subtypes driven by distinct molecular, epigenetic and mutational mechanisms, leading to formation of proneural, neural, classical and mesenchymal tumours. Moreover, molecularly distinct clonal cellular lineages co-exist within individual GBM lesions, where they differentiate according to distinct stem cell hierarchies resulting in several facets of tumour heterogeneity and the related potential for intercellular interactions. Glioma stem cells (GSCs) may carry signatures of either proneural or mesenchymal GBM subtypes and differ in several biological characteristics that are, at least in part, represented by the output and repertoire of EV production (vesiculome). We report that vesiculomes differ between known GBM subtypes. EVs may also reflect and influence the equilibrium of the stem cell hierarchy, contain oncogenic drivers and modulate the microenvironment (vascular niche). The GBM/GSC subtype-specific differentials in EV cargo of proteins, transcripts, microRNA and DNA may enable detection of the dynamics of the stem cell compartment and result in biological effects that remain to be fully characterized.

Authors+Show Affiliations

Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States. Electronic address: Ichiro.nakano@osumc.edu.McGill University, Montreal Children's Hospital, RI MUHC, Montreal, Quebec, Canada.Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.McGill University, Montreal Children's Hospital, RI MUHC, Montreal, Quebec, Canada. Electronic address: janusz.rak@mcgill.ca.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25721810

Citation

Nakano, Ichiro, et al. "Extracellular Vesicles in the Biology of Brain Tumour Stem cells--Implications for Inter-cellular Communication, Therapy and Biomarker Development." Seminars in Cell & Developmental Biology, vol. 40, 2015, pp. 17-26.
Nakano I, Garnier D, Minata M, et al. Extracellular vesicles in the biology of brain tumour stem cells--Implications for inter-cellular communication, therapy and biomarker development. Semin Cell Dev Biol. 2015;40:17-26.
Nakano, I., Garnier, D., Minata, M., & Rak, J. (2015). Extracellular vesicles in the biology of brain tumour stem cells--Implications for inter-cellular communication, therapy and biomarker development. Seminars in Cell & Developmental Biology, 40, pp. 17-26. doi:10.1016/j.semcdb.2015.02.011.
Nakano I, et al. Extracellular Vesicles in the Biology of Brain Tumour Stem cells--Implications for Inter-cellular Communication, Therapy and Biomarker Development. Semin Cell Dev Biol. 2015;40:17-26. PubMed PMID: 25721810.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular vesicles in the biology of brain tumour stem cells--Implications for inter-cellular communication, therapy and biomarker development. AU - Nakano,Ichiro, AU - Garnier,Delphine, AU - Minata,Mutsuko, AU - Rak,Janusz, Y1 - 2015/02/23/ PY - 2014/09/24/received PY - 2015/02/17/revised PY - 2015/02/17/accepted PY - 2015/2/28/entrez PY - 2015/2/28/pubmed PY - 2015/12/24/medline KW - Cancer KW - Exosomes KW - Extracellular vesicles KW - Glioblastoma KW - Glioma stem cells KW - Oncogenes SP - 17 EP - 26 JF - Seminars in cell & developmental biology JO - Semin. Cell Dev. Biol. VL - 40 N2 - Extracellular vesicles (EVs) act as carriers of molecular and oncogenic signatures present in subsets of tumour cells and tumour-associated stroma, and as mediators of intercellular communication. These processes likely involve cancer stem cells (CSCs). EVs represent a unique pathway of cellular export and cell-to-cell transfer of insoluble molecular regulators such as membrane receptors, signalling proteins and metabolites, thereby influencing the functional integration of cancer cell populations. While mechanisms that control biogenesis, cargo and uptake of different classes of EVs (exosomes, microvesicles, ectosomes, large oncosomes) are poorly understood, they likely remain under the influence of stress-responses, microenvironment and oncogenic processes that define the biology and heterogeneity of human cancers. In glioblastoma (GBM), recent molecular profiling approaches distinguished several disease subtypes driven by distinct molecular, epigenetic and mutational mechanisms, leading to formation of proneural, neural, classical and mesenchymal tumours. Moreover, molecularly distinct clonal cellular lineages co-exist within individual GBM lesions, where they differentiate according to distinct stem cell hierarchies resulting in several facets of tumour heterogeneity and the related potential for intercellular interactions. Glioma stem cells (GSCs) may carry signatures of either proneural or mesenchymal GBM subtypes and differ in several biological characteristics that are, at least in part, represented by the output and repertoire of EV production (vesiculome). We report that vesiculomes differ between known GBM subtypes. EVs may also reflect and influence the equilibrium of the stem cell hierarchy, contain oncogenic drivers and modulate the microenvironment (vascular niche). The GBM/GSC subtype-specific differentials in EV cargo of proteins, transcripts, microRNA and DNA may enable detection of the dynamics of the stem cell compartment and result in biological effects that remain to be fully characterized. SN - 1096-3634 UR - https://www.unboundmedicine.com/medline/citation/25721810/Extracellular_vesicles_in_the_biology_of_brain_tumour_stem_cells__Implications_for_inter_cellular_communication_therapy_and_biomarker_development_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1084-9521(15)00038-5 DB - PRIME DP - Unbound Medicine ER -