title: Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood-brain barrier.
abstract: We have investigated the role of the Rho/ROCK signaling pathway in the interaction of metastatic melanoma cells with the brain endothelium. ROCK inhibition induced a shift of melanoma cells to the mesenchymal phenotype, increased the number of melanoma cells attached to the brain endothelium, and strengthened the adhesion force between melanoma and endothelial cells. Inhibition of ROCK raised the number of melanoma cells migrating through the brain endothelial monolayer and promoted the formation of parenchymal brain metastases in vivo. We have shown that inhibition of the Rho/ROCK pathway in melanoma, but not in brain endothelial cells, is responsible for this phenomenon. Our results indicate that the mesenchymal type of tumor cell movement is primordial in the transmigration of melanoma cells through the blood-brain barrier.
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Imola
authors.initials: I
authors.lastname: Wilhelm
authors.forename: Csilla
authors.initials: C
authors.lastname: Fazakas
authors.forename: Judit
authors.initials: J
authors.lastname: Molnár
authors.forename: János
authors.initials: J
authors.lastname: Haskó
authors.forename: Attila G
authors.initials: AG
authors.lastname: Végh
authors.forename: László
authors.initials: L
authors.lastname: Cervenak
authors.forename: Péter
authors.initials: P
authors.lastname: Nagyőszi
authors.forename: Adám
authors.initials: A
authors.lastname: Nyúl-Tóth
authors.forename: Attila E
authors.initials: AE
authors.lastname: Farkas
authors.forename: Hannelore
authors.initials: H
authors.lastname: Bauer
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Bauer
authors.forename: György
authors.initials: G
authors.lastname: Váró
authors.forename: István A
authors.initials: IA
authors.lastname: Krizbai
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000473:pathology; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D054460:rho-Associated Kinases
keywords: ROCK; Rho; blood-brain barrier; cerebral endothelial cell; melanoma; metastasis