Targeting cholesterol transport in circulating melanoma cells to  inhibit metastasis

This study investigates whether targeting cholesterol transport in melanoma CTCs can retard metastasis development. Nanolipolee‐007, the liposomal form of leelamine, reduced melanoma metastasis in both a novel in vitro flow system mimicking the circulating system and in experimental as well as spontaneous animal metastasis models, irrespective of the BRAF mutational status of the CTCs. Leelamine led to cholesterol trapping in lysosomes, which subsequently shut down receptor‐mediated endocytosis, endosome trafficking, and inhibited the major oncogenic signaling cascades important for survival such as the AKT pathway. As pAKT is important in CTC survival, inhibition by targeting cholesterol metabolism led to apoptosis, suggesting this approach might be particularly effective for those CTCs having high levels of pAKT to aid survival in the circulation system.
Source: Pigment Cell Research - Category: Cytology Authors: Tags: ORIGINAL ARTICLE Source Type: research