title: Inhibition of collagen XVI expression reduces glioma cell invasiveness.
abstract: Glioblastomas are characterized by an intense local invasiveness that limits surgical resection. One mechanism by which glioma cells enforce their migration into brain tissue is reorganization of tumour associated extracellular matrix (ECM). Collagen XVI is a minor component of connective tissues. However, in glioblastoma tissue it is dramatically upregulated compared to the ECM of normal cortex. The aim of this study is to delineate tumour cell invasion and underlying mechanisms involving collagen XVI by using a siRNA mediated collagen XVI knockdown model in U87MG human glioblastoma cells. Knockdown of collagen XVI resulted in decreased invasiveness in Boyden chamber assays, and in a reduction of focal adhesion contact numbers per cell. Gene expression was upregulated for protocadherin 18 and downregulated for kindlin-1 and -2. Proliferation was not affected while flow cytometric analysis demonstrated reduced β1-integrin activation in collagen XVI knockdown cells. We suggest that in glioblastoma tissue collagen XVI may impair the cell-cell interaction in favour of enhancement of invasion. The modification of the β1-integrin activation pattern through collagen XVI might be a molecular mechanism to further augment the invasive phenotype of glioma cells. Elucidating the underlying mechanisms of glioma cell invasion promoted by collagen XVI may provide novel cancer therapeutic approaches in neurooncology.
authors.affiliation: Dept of Orthopaedics, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Bauer
authors.forename: Sabine
authors.initials: S
authors.lastname: Ratzinger
authors.forename: Lynn
authors.initials: L
authors.lastname: Wales
authors.forename: Anja
authors.initials: A
authors.lastname: Bosserhoff
authors.forename: Volker
authors.initials: V
authors.lastname: Senner
authors.forename: Joachim
authors.initials: J
authors.lastname: Grifka
authors.forename: Susanne
authors.initials: S
authors.lastname: Grässel
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D000091363:Protocadherins; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C481130:COL16A1 protein, human; D015820:Cadherins; C475301:FERMT1 protein, human; C477322:FERMT3 protein, human; D019012:Integrin beta1; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C438604:PCDH18 protein, human; D000091363:Protocadherins; D034741:RNA, Small Interfering; D003094:Collagen