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

doi:10.1111/pcmr.12169

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 journal › Article › peer-review

20 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 language	English
Pages (from-to)	113-123
Number of pages	11
Journal	Pigment Cell and Melanoma Research
Volume	27
Issue number	1
DOIs	https://doi.org/10.1111/pcmr.12169
Publication status	Published - Jan 2014

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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

@article{d9525a62fb4d4174b15bbf46af181a91,

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.",

author = "Imola Wilhelm and Csilla Fazakas and Judit Moln{\'a}r and J{\'a}nos Hask{\'o} and V{\'e}gh, {Attila G.} and L{\'a}szl{\'o} Cervenak and P{\'e}ter Nagyoszi and {\'A}d{\'a}m Ny{\'u}l-T{\'o}th and Farkas, {Attila E.} and Hannelore Bauer and Guillemin, {Gilles J.} and Bauer, {Hans Christian} and Gy{\"o}rgy V{\'a}r{\'o} and Krizbai, {Istv{\'a}n A.}",

year = "2014",

month = jan,

doi = "10.1111/pcmr.12169",

language = "English",

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pages = "113--123",

journal = "Pigment Cell and Melanoma Research",

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Wilhelm, I, Fazakas, C, Molnár, J, Haskó, J, Végh, AG, Cervenak, L, Nagyoszi, P, Nyúl-Tóth, Á, Farkas, AE, Bauer, H, Guillemin, GJ, Bauer, HC, Váró, G & Krizbai, IA 2014, 'Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood-brain barrier', Pigment Cell and Melanoma Research, vol. 27, no. 1, pp. 113-123. https://doi.org/10.1111/pcmr.12169

TY - JOUR

T1 - Role of Rho/ROCK signaling in the interaction of melanoma cells with the blood-brain barrier

AU - Wilhelm, Imola

AU - Fazakas, Csilla

AU - Molnár, Judit

AU - Haskó, János

AU - Végh, Attila G.

AU - Cervenak, László

AU - Nagyoszi, Péter

AU - Nyúl-Tóth, Ádám

AU - Farkas, Attila E.

AU - Bauer, Hannelore

AU - Guillemin, Gilles J.

AU - Bauer, Hans Christian

AU - Váró, György

AU - Krizbai, István A.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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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U2 - 10.1111/pcmr.12169

DO - 10.1111/pcmr.12169

M3 - Article

C2 - 24148763

AN - SCOPUS:84890798337

SN - 1755-1471

VL - 27

SP - 113

EP - 123

JO - Pigment Cell and Melanoma Research

JF - Pigment Cell and Melanoma Research

IS - 1

ER -

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

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