Abstract 481: The role of jaspamide in the actin cytoskeleton of melanoma cells: The relation between migration and invasion

Abstract

Abstract Metastasis is the leading cause of melanoma mortality. The metastatic cascade represents a multi-step process which includes several cellular and molecular processes including cell migration and invasion. Tumor cells can migrate either collectively, in a mesenchymal or in an amoeboid type of movement. The role of microfilaments is essential in mesenchymal migration, where it acts in the formation of membrane protrusions, and amoeboid migration, where they play a key role in cell contraction. In this context, the present work aimed to analyze the effects of the marine sponge-derived drug jaspamide, which has well-known properties on cytoskeleton (anti-polymerizing of the actin microfilaments). After the determination of the IC50 concentrations for the HT144 (derived from human melanoma) and NGM (from human benign nevus) cell lines, the effects of the treatment with jaspamide were studied through wound assays, transwell assays, Boyden's chamber assays, fluorescent cytochemistry, immunofluorescence and Western blotting. The treatments demonstrated the drug acts disorganizing the microfilament cytoskeleton in a dose-dependent way, leading the accumulation of F-actin in the perinuclear region. The wound assays indicated that drug treatment impaired the migration ability of both cell lines. However assays in Boyden's chambers showed increasing in cell migration in consequence of jaspamide treatment, result that could be explained by switch of the migration strategy from mesenchymal to ameboid. This fact was corroborated by the decreased expression of the IRSp53 protein after jaspamide treatment meanwhile MT1-MMP expression is not affected by the treatment. By treating thecell lines with the compounds Y-27632 or NSC23766 in addition to jaspamide, it is possible to conclude that NGM cells use mainly the RAc signaling pathway to control cellular migration process. In contrast, the melanoma cell line HT144 however could use either Rac or Rho pathway to migrate. Key words: Melanoma. Jaspamide. Migration. Invasion. Metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 481. doi:1538-7445.AM2012-481