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

Research output: Contribution to journalArticle

14 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 1 2014

Keywords

  • Blood-brain barrier
  • Cerebral endothelial cell
  • Melanoma
  • Metastasis
  • ROCK
  • Rho

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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  • Cite this

    Wilhelm, I., Fazakas, C., Molnár, J., Haskó, J., Végh, A. G., Cervenak, L., Nagyoszi, P., Nyúl-Tóth, Á., Farkas, A. E., Bauer, H., Guillemin, G. J., Bauer, H. C., Váró, G., & Krizbai, I. A. (2014). Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood-brain barrier. Pigment Cell and Melanoma Research, 27(1), 113-123. https://doi.org/10.1111/pcmr.12169