Hepatic Endothelial Cells May Assist Uveal Melanomas to Target the Liver Through alpha-4 integrin and VCAM-1 Interactions

Abstract

Abstract: : Purpose: To investigate adhesive interactions of invasive and non-invasive uveal melanomas with hepatic and dermal endothelial cells. Methods: Using an invasive and a non-invasive uveal melanoma cell line, tumour cells were cultured with either hepatic or dermal endothelial conditioned media or cells for 24 hours. For co-culture experiments, endothelial cells were pre-labeled with a fluorescent probe, allowing selective dissociation. Cells were then assessed by flow cytometry for changes in adhesion molecule expression. Results: Both soluble endothelial cell factors and direct contact with the endothelium regulated levels of adhesion molecule expression. The pattern of regulation further varied between the two uveal melanoma cell types and the two endothelial cell types. Direct contact of invasive uveal melanoma cells with hepatic but not dermal endothelial cells resulted in an increase in tumour α4-integrin expression and its endothelial ligand, VCAM-1. This effect was not observed by the non-invasive cells, or after culture with endothelial conditioned media. Conclusions: Metastatic uveal melanomas predominantly target the liver. As endothelial cells from different organs display diverse structural and biochemical characteristics, it is possible that hepatic endothelial cells assist liver targeting. The α4-VCAM-1 interaction may play a significant role in this process. Supported by The Humane Research Trust and Yorkshire Cancer Research.

Keywords: cell adhesions/cell junctions • flow cytometry • melanoma