Abstract
Purpose :
Up to 50% of uveal melanoma (UM) patients develop metastasis, which is lethal. Thus, understanding how cancer dissemination occurs is crucial for diagnosis, prognosis, and treatment. EVs derived from cancer cells have attracted interest due to their role as biomarkers as well as for their potential implications in cancer dissemination. EVs physicochemical characteristics regulate how particles interact within different microenvironments inside the human body, and thus may play a role in cancer dissemination. However, the physicochemical characteristics of EVs produced by UM cells is generally overlooked, especially zeta potential, which influences the biophysical interaction between vesicles and cells, with direct implications on uptake. In this work, we characterized the size, size distribution, and the zeta potential of EVs derived from UM cell lines and non-cancerous cells.
Methods :
EVs derived from 3 primary UM cell lines (MP41, MP46, OCM), a metastatic (OMM2.5) UM cell line and fibroblasts (HTB 102) as control were extracted by ultracentrifugation. EV size and size distribution were characterized using Dynamic Light Scattering (DLS). The zeta potential of EVs was calculated from their electrophoretic mobility.
Results :
EV diameter can be grouped in 4 different size sets. 1) Normal fibroblasts showed the smallest EV’s diameter (137.7 nm) alongside the broadest size distribution. 2) MP41 demonstrated the narrowest size distribution with a size of 166 nm. 3) EVs derived from MP46, and OCM cell lines have similar dimensions (198 and 195 nm respectively); however, OCM-derived EVs showed a less monodisperse population. 4) Interestingly, metastatic cells (OMM2.5) had the largest diameter. In terms of zeta potential, most of the studied EVs showed a zeta potential close to neutral values, except for MP41 derived EVs, for which the zeta potential was found to be remarkably high and negative (-22.3 +/- 1.4 mV).
Conclusions :
Our work is the first complete analysis of the physicochemical characterization of EVs derived from UM cells. Our data shows a difference in the physicochemical features of EVs derived from primary and metastatic UM cell lines as well as non-cancerous cells. This work is a pioneer to better understand EVs role in UM dissemination and how these characteristics might affect biodistribution and cellular uptake. Further characterization from EVs should be investigated.
This is a 2020 ARVO Annual Meeting abstract.