title: Isolation and characterization of a population of stem-like progenitor cells from an atypical meningioma.
abstract: The majority of meningiomas are benign tumors associated with favorable outcomes; however, the less common aggressive variants with unfavorable outcomes often recur and may be due to subpopulations of less-differentiated cells residing within the tumor. These subpopulations of tumor cells have tumor-initiating properties and may be isolated from heterogeneous tumors when sorted or cultured in defined medium. We report the isolation and characterization of a population of tumor-initiating cells derived from an atypical meningioma. We identify a tumor-initiating population from an atypical meningioma, termed meningioma-initiating cells (MICs). These MICs self-renew, differentiate, and can recapitulate the histological characteristics of the parental tumor when transplanted at 1000 cells into the flank regions of athymic nude mice. Immunohistochemistry reveals stem-like protein expression patterns similar to neural stem and progenitor cells (NSPCs) while genomic profiling verified the isolation of cancer cells (with defined meningioma chromosomal aberrations) from the bulk tumor. Microarray and pathway analysis identifies biochemical processes and gene networks related to aberrant cell cycle progression, particularly the loss of heterozygosity of tumor suppressor genes CDKN2A (p16(INK4A)), p14(ARF), and CDKN2B (p15(INK4B)). Flow cytometric analysis revealed the expression of CD44 and activated leukocyte adhesion molecule (ALCAM/CD166); these may prove to be markers able to identify this cell type. The isolation and identification of a tumor-initiating cell population capable of forming meningiomas demonstrates a useful model for understanding meningioma development. This meningioma model may be used to study the cell hierarchy of meningioma tumorogenesis and provide increased understanding of malignant progression.
authors.affiliation: Division of Biological Sciences, College of Arts & Science, University of Missouri, Columbia, MO 65211, USA. rath@kennedykrieger.org
authors.forename: Prakash
authors.initials: P
authors.lastname: Rath
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
authors.forename: N Scott
authors.initials: NS
authors.lastname: Litofsky
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Anthony
authors.forename: Qi
authors.initials: Q
authors.lastname: Feng
authors.forename: Craig
authors.initials: C
authors.lastname: Franklin
authors.forename: Lirong
authors.initials: L
authors.lastname: Pei
authors.forename: Alan
authors.initials: A
authors.lastname: Free
authors.forename: Jimei
authors.initials: J
authors.lastname: Liu
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Ren
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kirk
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D016678:Genome / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D008579:Meningioma / Q000235:genetics / Q000473:pathology*; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008934:Mitogens / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D018960:Hyaluronan Receptors; D008934:Mitogens