In vivo GFP imaging of dormant liver metastasis in a human uveal melanoma mouse model

Abstract

Purpose: We previouly demonstrated the feasibility of a human uveal melanoma GFP model in nude mice. We were able to monitor the preferential colonization of the liver by malignant cells during a 20‐day period. In this study we extended the observation period in order to observe disease progression and metastatic growth. Methods: Five hundred thousand, GFP transfected, human primary uveal melanoma cells (92.1) were injected into the tail vein of 30 nude mice at time zero. Starting at day one, five mouse per week was imaged, using an abdominal incision to expose the liver, for up to 60 minutes before sacrifice. The liver was imaged in vivo and post mortem, while the lungs, spleen, and kidney were all examined post‐mortem for GFP expression. Histopathological examination of all organs was performed to ensure that the GFP signal was arising from malignant cells. Results: In vivo imaging of the liver revealed positive GFP signal in all mice throughout the experiment. Malignant cells seeded the liver after injection, but there was no apparent tumor growth upon completion of the experiment. The micrometastatic foci remained viable without changes in size or intensity of the signal. No tumors were seen in any other organ at the end of the experiment. Histopathology confirmed that the cells emitting GFP were malignant cells. Conclusions: The results of this uveal melanoma model show great promise for understanding the previously unobservable interactions between single human uveal melanoma cells and native liver tissue. The fact that our cells successfully colonize the liver yet remain dormant for six weeks should actually mirror the disease in humans; metastases in patients takes roughly five to ten years to develop.