title: Heterogeneous phenotype of human glioblastoma: in vitro study.
abstract: Glioblastomas (GBMs) are the most lethal primary brain tumours. Increasing evidence shows that brain tumours contain the population of stem cells, so-called cancer stem cells (CSCs). Stem cell marker CD133 was reported to identify CSC population in GBM. Further studies have indicated that CD133 negative cells exhibiting similar properties and are able to initiate the tumour, self-renew and undergo multilineage differentiation. GBM is a highly heterogeneous tumour and may contain different stem cell populations with different functional properties. We characterized five GBM cell lines, established from surgical samples, according to the marker expression, proliferation and differentiation potential. CD133 positive cell lines showed increased proliferation rate in neurosphere condition and marked differentiation potential towards neuronal lineages. Whereas two cell lines low-expressing CD133 marker showed mesenchymal properties in vitro, that is high proliferation rate in serum condition and differentiation in mesenchymal cell types. Further, we compared therapy resistance capacity of GBM cell lines treated with hydroxyurea. Our results suggest that CSC concept is more complex than it was believed before, and CD133 could not define entire stem cell population within GBM. At least two different subtypes of GBM CSCs exist, which may have different biological characteristics and imply different therapeutic strategies.
authors.affiliation: Neurosurgery, ASO CTO, OIRM S. Anna, Turin, Italy.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Denysenko
authors.forename: Luisa
authors.initials: L
authors.lastname: Gennero
authors.forename: Carola
authors.initials: C
authors.lastname: Juenemann
authors.forename: Isabella
authors.initials: I
authors.lastname: Morra
authors.forename: Paolo
authors.initials: P
authors.lastname: Masperi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ceroni
authors.forename: Antonella
authors.initials: A
authors.lastname: Pragliola
authors.forename: Antonio
authors.initials: A
authors.lastname: Ponzetto
authors.forename: Antonio
authors.initials: A
authors.lastname: Melcarne
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D018740:Genetic Heterogeneity; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D006918:Hydroxyurea
keywords: CD133; cancer stem cells; glioblastoma; glioblastoma subtypes; hydroxyurea