3D Spheroid Configurations Are Possible Indicators for Evaluating the Pathophysiology of Melanoma Cell Lines

This study examined how 3D spheroid morphology correlates with metabolic and genetic features in human malignant melanoma (MM) cell lines. Using five melanoma lines (WM266-4, SM2-1, A375, MM418, and SK-mel-24), the researchers observed distinct 3D architectures ranging from spherical to highly deformed spheroids. These geometric differences were linked to mitochondrial respiration, glycolytic capacity, and gene expression patterns. RNA-sequencing revealed KRAS and SOX2 as master regulators of spheroid shape diversity. Drug-resistant A375DT spheroids regained circularity with elevated metabolic activity, suggesting a coupling between 3D morphology, metabolic phenotype, and oncogenic signaling.