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Role of Rho/ ROCK signaling in the interaction of melanoma cells with the blood–brain barrier
Author(s) -
Wilhelm Imola,
Fazakas Csilla,
Molnár Judit,
Haskó János,
Végh Attila G.,
Cervenak László,
Nagyőszi Péter,
NyúlTóth Ádám,
Farkas Attila E.,
Bauer Hannelore,
Guillemin Gilles J.,
Bauer HansChristian,
Váró György,
Krizbai István A.
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12169
Subject(s) - melanoma , endothelium , mesenchymal stem cell , blood–brain barrier , parenchyma , cancer research , phenotype , endothelial stem cell , microbiology and biotechnology , in vivo , biology , chemistry , pathology , medicine , in vitro , neuroscience , central nervous system , endocrinology , gene , genetics
Summary We have investigated the role of the R ho/ 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.