title: Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level.
abstract: While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Klank
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Decker Grunke
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Bangasser
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Colleen L
authors.initials: CL
authors.lastname: Forster
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Price
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Odde
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: SantaCruz
authors.affiliation: Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rosenfeld
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.affiliation: Department of Oncology, London Health Science Center, Schulich School of Medicine & Dentistry, Western University, London, Ontario N6A 4L6, Canada.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Turley
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: McCarthy
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Ohlfest
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: oddex002@umn.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Odde
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D019895:Transposases / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D019895:Transposases
keywords: CD44; biphasic migration; biphasic survival; glioma