Pathological adhesion of primary human schwannoma cells is dependent on altered expression of integrins.
Mutations in the tumor suppressor gene coding for merlin cause Neurofibromatosis type 2 (NF2), all spontaneous schwannomas, and a majority of meningiomas. Merlin links transmembrane proteins to the cytoskeleton. Accordingly, primary human schwannoma cells lacking merlin show an increased number of lamellipodia and filopodia as well as increased cell spreading. We show enhanced adhesion in primary human schwannoma cells and present evidence that this is dependent on the integrin chains alpha6beta1 and alpha6beta4. We further demonstrate that the integrin chains beta1 and beta4 are upregulated in schwannomas using different complementary methods, and report higher expression of these integrins per schwannoma cell by fluorescence assisted cell sorting (FACS). Finally we report clustering of the integrin chains alpha6, beta1, and beta4 on schwannoma cells. Our findings fit well into recent data on the role of merlin in signaling cascades connected to integrins and help explain pathological ensheathment of extracellular matrix or pseudomesaxon formation which is a hallmark of schwannoma histopathology.
Utermark
Tamara
T
Department of Neurology, Zentrum für klinische Forschung, University of Ulm, Germany.
Kaempchen
Katherine
K
Hanemann
C Oliver
CO
D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D009442:Neurilemmoma / Q000378:metabolism / Q000473:pathology*; D016518:Neurofibromatosis 2; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation / Q000379:methods; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured
D016023:Integrins; D021122:Protein Subunits; D012333:RNA, Messenger; D012313:RNA