title: Interactive properties of human glioblastoma cells with brain neurons in culture and neuronal modulation of glial laminin organization.
abstract: The harmonious development of the central nervous system depends on the interactions of the neuronal and glial cells. Extracellular matrix elements play important roles in these interactions, especially laminin produced by astrocytes, which has been shown to be a good substrate for neuron growth and axonal guidance. Glioblastomas are the most common subtypes of primary brain tumors and may be astrocytes in origin. As normal laminin-producing glial cells are the preferential substrate for neurons, and glial tumors have been shown to produce laminin, we questioned whether glioblastoma retained the same normal glial-neuron interactive properties with respect to neuronal growth and differentiation. Then, rat neurons were co-cultured onto rat normal astrocytes or onto three human glioblastoma cell lines obtained from neurosurgery. The co-culture confirmed that human glioblastoma cells as well as astrocytes maintained the ability to support neuritogenesis, but non-neural normal or tumoral cells failed to do so. However, glioblastoma cells did not distinguish embryonic from post-natal neurons in relation to neurite pattern in the co-cultures, as normal astrocytes did. Further, the laminin organization on both normal and tumoral glial cells was altered from a filamentous arrangement to a mixed punctuate/filamentous pattern when in co-culture with neurons. Together, these results suggest that glioblastoma cells could identify neuronal cells as partners, to support their growth and induce complex neurites, but they lost the normal glia property to distinguish neuronal age. In addition, our results show for the first time that neurons modulate the organization of astrocytes and glioblastoma laminin on the extracellular matrix.
authors.affiliation: Departamento de Anatomia, Universidade Federal do Rio de Janeiro, Bloco F sala 20, Rio de Janeiro 21949-590, Brazil.
authors.forename: Jane
authors.initials: J
authors.lastname: Faria
authors.forename: Luciana
authors.initials: L
authors.lastname: Romão
authors.forename: Sheila
authors.initials: S
authors.lastname: Martins
authors.forename: Tércia
authors.initials: T
authors.lastname: Alves
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Mendes
authors.forename: Giselle Pinto
authors.initials: GP
authors.lastname: de Faria
authors.forename: Rosenilde
authors.initials: R
authors.lastname: Hollanda
authors.forename: Christina
authors.initials: C
authors.lastname: Takiya
authors.forename: Leila
authors.initials: L
authors.lastname: Chimelli
authors.forename: Veronica
authors.initials: V
authors.lastname: Morandi
authors.forename: Jorge Marcondes
authors.initials: JM
authors.lastname: de Souza
authors.forename: Jose Garcia
authors.initials: JG
authors.lastname: Abreu
authors.forename: Vivaldo
authors.initials: V
authors.lastname: Moura Neto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D001921:Brain / Q000166:cytology*; D001932:Brain Neoplasms / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005909:Glioblastoma / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007797:Laminin / Q000032:analysis*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007797:Laminin