Primary glioblastomas express mesenchymal stem-like properties.
Glioblastoma is the most common and aggressive primary brain cancer. Recent isolation and characterization of brain tumor-initiating cells supports the concept that transformed neural stem cells may seed glioblastoma. We previously identified a wide array of mesenchymal tissue transcripts overexpressed in a broad set of primary glioblastoma (de novo) tumors but not in secondary glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal brain tissues. Here, we extend this observation and show that a subset of primary glioblastoma tumors and their derived tumor lines express cellular and molecular markers that are associated with mesenchymal stem cells (MSC) and that glioblastoma cell cultures can be induced to differentiate into multiple mesenchymal lineage-like cell types. These findings suggest either that a subset of primary glioblastomas derive from transformed stem cells containing MSC-like properties and retain partial phenotypic aspects of a MSC nature in tumors or that glioblastomas activate a series of genes that result in mesenchymal properties of the cancer cells to effect sustained tumor growth and malignant progression.
Tso
Cho-Lea
CL
Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Room 5506, 695 Young Drive South, Los Angeles, CA 90095, USA.
Shintaku
Peter
P
Chen
James
J
Liu
Qinghai
Q
Liu
Jason
J
Chen
Zugen
Z
Yoshimoto
Koji
K
Mischel
Paul S
PS
Cloughesy
Timothy F
TF
Liau
Linda M
LM
Nelson
Stanley F
SF
D000954:Antigens, Surface / Q000096:biosynthesis; D001706:Biopsy; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry / Q000379:methods; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019656:Loss of Heterozygosity / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000473:pathology*; D009473:Neuronal Plasticity; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000954:Antigens, Surface