UCSF

The low efficacy of existing methods of treatment for late-stage melanoma has been attributed to the development of drug resistant cells. Following conventional treatments, enrichment of slowly cycling melanoma cells has been reported. Recently, a unique biological marker histone 3 K4 demethylase JARID1B was used to characterize slow-cycling cells within a rapidly proliferating population of melanoma cells. High JARID1B expression is almost exclusive to slow-cycling melanoma cells. This phenotype of cells has been shown to be temporarily distinct, dynamic, and necessary for continuous tumor growth. This study aims to seek metabolic changes between JARID1Bhigh subpopulations and bulk melanoma tumor cells. Targeting this subpopulation of drug resistant cells may improve the efficacy of existing treatments.

This project aims to identify and quantify metabolic differences by analyzing H NMR spectral data of cell extracts and culture media of slow-cycling JARID1Bhigh melanoma cells in comparison to highly proliferating bulk melanoma cells. We have demonstrated great improvement in acquiring consistent data for H NMR analysis over previous attempts. Our results show enhanced glucose and glutamine consumption, increased lactate/alanine ratios, and elevated concentrations of myo-inositol and choline derivatives in slow-cycling J/EGFPhigh subpopulations compared to highly proliferative tumor cells. These preliminary findings suggest heightened metabolic versatility in slow-cycling melanoma cells in accordance with recent revisions of cancer metabolism and may help understand the dynamic stem-ness of these seemingly quiescent cells.