Abstract
Purpose :
Uveal melanoma is a deadly cancer with high metastatic potential. Mitochondrial metabolism and epigenetics are known to play a role in tumorigenesis, progression, and metastasis. However, primary human uveal melanocytes are difficult to obtain, and the metabolic state of malignant versus benign uveal melanocytes has not been well characterized. We describe the morphologic patterns, growth rate, and mitochondrial function of uveal melanoma cell lines compared with successfully isolated primary human uveal melanocytes.
Methods :
Primary human uveal melanocytes were isolated from six donor eyes and successfully propagated in 2D cell culture. Photographs were obtained using inverted microscopy. Growth curves were determined using timed seeding and counting. Oxygen consumption under four respiratory states was measured using Seahorse. These were compared with two uveal melanoma cell lines, MP46 (highly adherent), and MP65 (partially suspended). Student t-test and its derivatives were used for statistical analysis as appropriate.
Results :
In 2D cell culture, uveal melanoma MP46 and MP65 cell lines formed primitive colonies with light to moderate pigmentation, while primary uveal melanocytes formed higher order patterns with heavy pigmentation. In addition, uveal melanoma MP46 cells grew faster than PK3 and PK4 benign melanocytes. Metabolically, uveal melanoma MP46 cells showed a glycolytic metabolic profile with statistically significant decrease in basal respiration, increase in proton leak respiration, and decrease in coupling efficiency when compared with PK4 primary uveal melanocytes.
Conclusions :
Uveal melanoma cell lines showed distinct morphological, physiologic, and metabolic characteristics compared with benign uveal melanocytes. Interestingly, despite increased growth rate, MP46 uveal melanoma cells showed decreased coupling efficiency compared with PK4 primary uveal melanocytes.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.