title: Dissecting the inter-substrate navigation of migrating glioblastoma cells with the stripe assay reveals a causative role of ROCK.
abstract: A hallmark of gliomas is the growth and migration of cells over long distances within the brain and proliferation within selected niches, indicating that the migrating cells navigate between complex substrates. We demonstrate in the present study a differential preference for migration that depends on Rho-associated coil kinase (ROCK) signaling, using the alternating Bonhoeffer stripe assay. Membrane fractions from nonmyelinated and myelinated brain areas from female rats, purified myelin also from female rats, and commercial extracellular matrix were used as substrates, with each substrate being tested against the others. The human tumor cell lines exhibited a clear preference for extracellular matrix over all other substrates and for myelinated over nonmyelinated tissue. ROCK signaling was different when cells were cultured on either substrate. The ROCK inhibitor Y27632 significantly attenuated and neutralized the preference for extracellular matrix and myelin, indicating that ROCK controls the substrate selectivity. The findings of this study pave the way for navigation-targeted therapeutics.
authors: Institute of Experimental Ophthalmology, School of Medicine, Westfalian-Wilhelms University, Albert Schweitzer Campus 1, Building D15, 48149, Münster, Germany. Sonja.Mertsch@ukmuenster.de
authors: Sonja
authors: S
authors: Mertsch
authors: Patrick
authors: P
authors: Oellers
authors: Michael
authors: M
authors: Wendling
authors: Werner
authors: W
authors: Stracke
authors: Solon
authors: S
authors: Thanos
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D013379:Substrate Specificity; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D054460:rho-Associated Kinases