title: Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status.
abstract: Glioblastoma cells exhibit highly invasive behavior whose mechanisms are not yet fully understood. The present study explores the relationship between the invasion capacity of 5 glioblastoma cell lines differing in p53 and PTEN status, expression of mTOR and several other marker proteins involved in cell invasion, actin cytoskeleton organization and cell morphology. We found that two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) exhibited the highest invasion rates through the Matrigel or collagen matrix. In DK-MG (p53wt/PTENwt) and GaMG (p53mut/PTENwt) cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG (p53wt/PTENmut), U373-MG and SNB19 (both p53mut/PTENmut) cells preferentially expressed F-actin in filopodia and lamellipodia. Scanning electron microscopy confirmed the abundant filopodia and lamellipodia in the PTEN mutated cell lines. Interestingly, the gene profiling analysis revealed two clusters of cell lines, corresponding to the most (U373-MG and SNB19, i.e. p53 and PTEN mutated cells) and less invasive phenotypes. The results of this study might shed new light on the mechanisms of glioblastoma invasion.
authors.affiliation: Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany. Electronic address: djuzenova_t@ukw.de.
authors.forename: Cholpon S
authors.initials: CS
authors.lastname: Djuzenova
authors.affiliation: Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fiedler
authors.affiliation: Lehrstuhl für Biotechnologie und Biophysik, Universität Würzburg, Biozentrum Am Hubland, 97070 Würzburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Memmel
authors.affiliation: Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Katzer
authors.affiliation: Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Elektronenmikroskopie, Biozentrum, Universität Würzburg, Am Hubland, 97070 Würzburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Krohne
authors.affiliation: Hauptabteilung Biophysik & Kryotechnologie, Fraunhofer-Institut für Biomedizinische Technik, Lehrstuhl für Molekulare und Zelluläre Biotechnologie/Nanotechnologie, Universität des Saarlandes, Ensheimer Strasse 48, 66386 St. Ingbert, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: Interdisciplinary Center for Clinical Research, University Hospital, Versbacher Strasse 7, 97078 Würzburg, Germany.
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.affiliation: Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Bülent
authors.initials: B
authors.lastname: Polat
authors.affiliation: Department of Radiation Oncology, University Hospital, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
authors.affiliation: Lehrstuhl für Biotechnologie und Biophysik, Universität Würzburg, Biozentrum Am Hubland, 97070 Würzburg, Germany.
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Sukhorukov
mesh_terms: D008841:Actin Cytoskeleton; D000199:Actins / Q000096:biosynthesis; D052160:Benzothiazoles / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D052160:Benzothiazoles; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; D014050:Toluene; D016159:Tumor Suppressor Protein p53; C121565:pifithrin; C546842:MTOR protein, human; C494929:PTEN protein, human
keywords: Actin remodeling; Cell adhesion; Cell matrix; Matrix-metalloprotease; Stress fibers