title: Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting.
abstract: Glioblastoma (GBM) is the most frequent and malignant brain tumor with an overall survival of only 14.6 months. Although these tumors are treated with surgery, radiation and chemotherapy, recurrence is inevitable. A critical population of tumor cells in terms of therapy, the so-called cancer stem cells (CSCs), has been identified in gliomas and many other cancers. These tumor cells have a stem cell-like phenotype and are suggested to be responsible for tumor growth, chemo- and radio-resistance as well as recurrence. However, functional evidence for migrating glioma cells having a stem cell-like phenotype is currently lacking. In the present study, the aim was to characterize the phenotype of migrating tumor cells using a novel migration assay based on serum-free stem cell medium and patient-derived spheroid cultures. The results showed pronounced migration of five different GBM spheroid cultures, but not of the commercial cell line U87MG. An in vitro limiting dilution assay showed preserved but reduced spheroid formation capacity of migrating cells. Orthotopic xenografting in mice showed preserved but reduced tumorigenic capacity. Profiling of mRNAs revealed no significant deregulation of 16 predefined CSC-related genes and the HOX-gene list in migrating cells compared to spheroids. Determination of GBM molecular subtypes revealed that subtypes of spheroids and migrating cells were identical. In conclusion, migrating tumor cells preserve expression of stem cell markers and functional CSC characteristics. Since CSCs are reported to be highly resistant to therapy, these results emphasize that the CSC phenotype should be taken into consideration in future treatment of GBMs.
authors: Department of Neurosurgery, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark. sune.munthe@rsyd.dk.|Department of Pathology, Odense University Hospital, Winsloew parken 15, 5000, Odense, Denmark. sune.munthe@rsyd.dk.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. sune.munthe@rsyd.dk.
authors: Sune
authors: S
authors: Munthe
authors: Department of Pathology, Odense University Hospital, Winsloew parken 15, 5000, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors: Mia D
authors: MD
authors: Sørensen
authors: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Mads
authors: M
authors: Thomassen
authors: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Mark
authors: M
authors: Burton
authors: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Torben A
authors: TA
authors: Kruse
authors: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.|Department of Cellular and Molecular Medicine, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA.
authors: Justin D
authors: JD
authors: Lathia
authors: Department of Neurosurgery, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors: Frantz Rom
authors: FR
authors: Poulsen
authors: Department of Pathology, Odense University Hospital, Winsloew parken 15, 5000, Odense, Denmark. bjarne.winther.kristensen@rsyd.dk.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. bjarne.winther.kristensen@rsyd.dk.
authors: Bjarne Winther
authors: BW
authors: Kristensen
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000401:mortality / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D046228:Microarray Analysis; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D018874:Spheroids, Cellular; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D016895:Culture Media, Serum-Free; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors
keywords: Cancer stem cell; Glioblastoma; Invasion; Migration