Abstract
Small cell lung cancer (SCLC) cells migration across human brain microvascular endothelial cells (HBMECs) is an essential step of brain metastases. Here we investigated signalling pathways in HBMECs contributing to the process. Inhibition of endothelial Rho kinase (ROCK) with Y27632 and overexpression of ROCK dominant-negative mutant prevented SCLC cells, NCI-H209, transendothelial migration and the concomitant changes of tight junction. Conversely, inhibition of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) had no effects. Furthermore, endothelial RhoA protein was activated during NCI-H209 cells transendothelial migration. Rho/ROCK participated in NCI-H209 cells transendothelial migration through regulating actin cytoskeleton reorganization. These results suggested that Rho/ROCK was required for SCLC cells transendothelial migration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / pharmacology
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology
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Brain Neoplasms / secondary
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Carcinoma, Small Cell / genetics
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Carcinoma, Small Cell / metabolism*
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Carcinoma, Small Cell / pathology
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Cell Line, Tumor
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Cell Movement* / drug effects
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Cell Movement* / genetics
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Cytoskeleton / genetics
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Cytoskeleton / metabolism
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Endothelial Cells / metabolism
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Endothelial Cells / pathology
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Genes, Dominant / genetics
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Humans
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Intracellular Signaling Peptides and Proteins
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism*
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Lung Neoplasms / pathology
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Neoplasm Metastasis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Pyridines / pharmacology
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Signal Transduction* / drug effects
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Signal Transduction* / genetics
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rho-Associated Kinases
Substances
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Amides
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Neoplasm Proteins
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Pyridines
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Y 27632
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Protein Serine-Threonine Kinases
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rho-Associated Kinases