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

Wilhelm, Imola Mária and Fazakas, Csilla and Molnár, Judit and Haskó, János and Végh, Attila Gergely and Cervenak, László and Nagyőszi, Péter and Nyúl-Tóth, Ádám and Farkas, Elek Attila and Bauer, Hannelore and Guillemin, Gilles J. and Bauer, Hans-Christian and Váró, György and Krizbai, István Adorján (2014) Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood-brain barrier. PIGMENT CELL AND MELANOMA RESEARCH, 27 (1). pp. 113-123. ISSN 1755-1471

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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.

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