Abstract 4199: Riluzole modulates the production of exosomes in melanoma cells

Abstract

Abstract Exosomes are naturally occurring small membrane enclosed microvesicles generated constitutively and released by various cell types and more frequently released by tumor cells. It was postulated that exosomes may facilitate communication within the local microenvironment and the primary tumor, supporting melanoma cell dissemination and early events in metastasis. A gain-of-function mutation of a neuronal receptor, metabotropic glutamate receptor 1 (GRM1), when ectopically expressed in melanocytes, was sufficient to induce in vitro melanocytic transformation and spontaneous malignant melanoma development in vivo in a transgenic mouse model. Normal mouse melanocytes transformed with an expression vector containing GRM1 showed production and secretion of exosomes confirmed by electron microscopy, while the parental normal melanocytes showed no detectable presence of exosomes. In light of this data, It was hypothesized that over-expression of GRM1 in melanoma cells normally expressing a moderate amount of the protein, may promote elevated levels of exosome formation, while inhibitors to the receptor or limiting the levels of available ligand may suppress exosome production. Preliminary results demonstrated the working hypothesis is correct. Our earlier studies showed that inhibitors of the receptor modulated GRM1-mediated signaling events interfere with downstream effectors resulting in a decrease in both cell proliferation in vitro and tumor progression in vivo. It is not known if GRM1 acts directly, via its signaling cascade, or by another route, on exosome production regulation, this will be investigated. In addition to the pharmacological inhibitors we will also use a genetic approach with silencing RNA to modulate GRM1 expression levels. Citation Format: Allison L. Isola, Yvonne Wen, James Goydos, Suzie Chen. Riluzole modulates the production of exosomes in melanoma cells. [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 4199. doi:10.1158/1538-7445.AM2014-4199