title: Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental ENU-induced gliomas.
abstract: Nestin+cells from spheroid aggregates display typical histopathological features compatible with cell stemness. Nestin and CD133+cells found in glioblastomas, distributed frequently around aberrant vessels, are considered as potential cancer stem cells. They are possible targets for antitumoral therapy because they lead the tumorigenesis, invasiveness and angiogenesis. However, little is known about their role and presence in low-grade gliomas. The aim of this work is to localize and characterize the distribution of these cells inside tumors during the development of experimental endogenous glioma. For this study, a single dose of Ethyl-nitrosourea was injected into pregnant rats. Double immunofluorescences were performed in order to identify stem-like and differentiated cells. Low-grade gliomas display Nestin+cells distributed throughout the tumor. More malignant gliomas show, in addition to that, a perivascular location with some Nestin+cells co-expressing CD133 or VEGF, and the intratumoral spheroid aggregates of Nestin/CD133+cells. These structures are encapsulated by well-differentiated VEGF/GFAP+cells. Spheroid aggregates increase in size in the most malignant stages. Spheroid aggregates have morphological and phenotypic similarities to in vitro neurospheres and could be an in vivo analogue of them. These arrangements could be a reservoir of undifferentiated cells formed to escape adverse microenvironments.
authors.affiliation: Laboratory for Clinical and Experimental Neuroscience (LaNCE), Department of Neuroscience, University of the Basque Country, Leioa, Spain. algarblandom@gmail.com.
authors.forename: Alvaro
authors.initials: A
authors.lastname: García-Blanco
authors.affiliation: LaNCE, Department of Nursing I, University of the Basque Country, Leioa Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Bulnes
authors.affiliation: LaNCE, Department of Surgery, University of the Basque Country and Neurosurgery Department, Cruces University Hospital, Bilbao, Spain.|Group Nanoneurosurgery, Institut of Health Research Biocruces, Barakaldo, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Pomposo
authors.affiliation: LaNCE, Department of Surgery, University of the Basque Country and Neurosurgery Department, Cruces University Hospital, Bilbao, Spain.|Group Nanoneurosurgery, Institut of Health Research Biocruces, Barakaldo, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Carrasco
authors.affiliation: Laboratory for Clinical and Experimental Neuroscience (LaNCE), Department of Neuroscience, University of the Basque Country, Leioa, Spain.|Group Nanoneurosurgery, Institut of Health Research Biocruces, Barakaldo, Spain.|Faculty of Health Science, Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Lafuente
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000473:pathology*; D002273:Carcinogens / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D005910:Glioma / Q000473:pathology*; D007150:Immunohistochemistry; D014411:Neoplastic Stem Cells / Q000473:pathology*; D064231:Nestin / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; C577486:Nes protein, rat; D064231:Nestin; D005038:Ethylnitrosourea