Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood-brain barrier

Imola Wilhelm, Csilla Fazakas, Judit Molnár, János Haskó, Attila G. Végh, László Cervenak, Péter Nagyoszi, Ádám Nyúl-Tóth, Attila E. Farkas, Hannelore Bauer, Gilles J. Guillemin, Hans Christian Bauer, György Váró, István A. Krizbai*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)113-123
    Number of pages11
    JournalPigment Cell and Melanoma Research
    Volume27
    Issue number1
    DOIs
    Publication statusPublished - Jan 2014

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