Abstract 5524: 5-aza-2′-deoxycytidine, a DNA demethylating agent, inhibits metastatic melanoma invasiveness

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 5524
• Main Authors: Etiévant, Chantal, Desjobert, Cécile, Carrier, Arnaud, Delmas, Audrey, Tost, Jorg, Favre, Gilles, Riond, Joelle, Arimondo, Paola
• Format: Journal Article
• Language: English
• Published: American Association for Cancer Research 01.10.2014
• Subjects: Cancer; Life Sciences
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-5524

Abstract Metastatic melanomas are the deadliest form of skin cancer and are very aggressive tumors showing highly invasive properties and a rapid chemoresistance to standard treatment (Dacarbazine) and to specific BRAF-V600E kinase inhibitors (Vemurafenib). Thus, targeting these tumors remains a major concern for novel therapeutic proposals. Abnormal patterns of DNA methylation, an epigenetic modification that cells use to control gene expression, have been described in these tumors. These epigenetic modifications participate in melanoma formation and maintenance. The aim of our project is to characterize the DNA methylation changes that occur in the most aggressive form of melanoma and to reverse these changes by using clinically active DNA methyltransferase inhibitors (5-aza-2′-deoxycytidine, 5-aza-dC). To date a limited number of datasets have been published depicting the effects of inhibitors of DNA methylation on invasive capacities of metastatic melanoma cells. The work presented here, focuses on the study of the effects of DNA methylation inhibition on metastatic melanoma invasiveness. We have set up an original method to quantify DNA methylation by FACS and shown that non cytotoxic nanomolar 5-aza-dC concentrations were able to demethylate DNA of WM-266-4 metastatic melanoma cells. Then using an in vitro 3D spheroids cell invasion assay and fluorescent microscopy to measure invasion capacities of metastatic cell lines, we showed that 5-aza-dC was able to inhibit invasion of WM-266-4 cells at these non-cytotoxic demethylating concentrations. Citation Format: Chantal Etiévant, Cécile Desjobert, Arnaud Carrier, Audrey Delmas, Jorg Tost, Gilles Favre, Joelle Riond, Paola Arimondo. 5-aza-2′-deoxycytidine, a DNA demethylating agent, inhibits metastatic melanoma invasiveness. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5524. doi:10.1158/1538-7445.AM2014-5524