Abstract 4304: Malignant melanoma cells with aggressive properties are common and not distinguishable by proposed markers for cancer stem cells

Abstract

Abstract In malignant melanoma, conflicting results have been reported regarding the presence of exclusive cells with enhanced aggressive properties, so called cancer stem cells (CSC), raising a doubt whether melanoma follows a CSC model and is hierarchically organized. By characterizing melanoma cells from short-term cell cultures, xenografts and patient biopsies, we aim to collect further evidence either to: i) support the existence of distinct CSC-like subpopulations, or ii) strengthen a notion about the common presence of cells demonstrating aggressive behavior and lack of cellular hierarchy in melanoma. By using individual-cell assays, we have shown that a large fraction (up to 60 %) of random single melanoma cells display high clonogenicity and self-renewal i.e. properties associated with tumorigenic potential. In search for a marker for such clonogenic/tumorigenic cells, we found that melanomas often harbor a large distinct subpopulation with elevated activity of Aldehyde Dehydrogenase (ALDH), a proposed marker for CSC-like cells in some hierarchically organized cancers. Interestingly, ALDH activity in melanoma patient biopsies seemed to correlate to the expression of melanoma-associated-antigen, HMW-MAA, which is linked to tumor progression. Furthermore, in vivo ALDH+ melanoma cells could convert to ALDH−, while the opposite conversion was rare, indicating a certain “cellular hierarchy” with respect to the ALDH phenotype. However, comparison of ALDH+ and ALDH− cells revealed that both subpopulations are highly clonogenic, tumorigenic and resistant to drugs proposed for melanoma therapy, DTIC and HGS-ETR2. This suggests that in malignant melanoma, ALDH, likewise earlier investigated “surface markers” of CSCs, does not distinguish cells with enhanced biological aggressiveness. In conclusion, melanoma cells exhibiting properties linked to aggressive phenotype are common and not restricted to subpopulations expressing proposed “CSC markers”, which contradicts the traditional view of CSCs. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4304.