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Mohamed Abdouh, Thupten Tsering, Julia Valdemarin Burnier, Paulina Garcia de Alba Graue, Goffredo Orazio Arena, Miguel N Burnier; Horizontal transfer of malignant traits via blood-derived extracellular vesicles of uveal melanoma patients. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2835.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) is the most common intraocular malignancy that arises from uveal tract-resident melanocytes. Its early diagnosis and treatment is crucial, as survival correlates with primary tumor size while metastasis is life threatening. Approximately 50% of patients will develop liver metastases with an overall survival of no more than 12 months. Recently, we showed that cancer circulating factors transited to susceptible target cells and induced their transformation. In the present study, we sought to determine the ability of UM derived extracellular vesicles (EVs) to transform target cells
BRCA1-deficient fibroblasts were exposed to EVs isolated from the serum of healthy volunteers and UM affected patients, and from cultures of UM cell lines and normal melanocytes. Treated cells were analyzed for cell proliferation in vitro and for their transformation following injection into NOD-SCID mice
EVs were characterized both physically and phenotypically by electron microscopy, Nanosight tracking analyses and the expression of specific EVs markers. Functionally, UM derived EVs induced a significant increase in cell proliferation while they did not affect cell viability. When we analyzed the behaviour of exposed cells following inoculation in mice, none of the mice injected with cells treated with control EVs was found to have grown tumors. In contrast, mice injected with cells exposed to EVs from two UM patients serum, and one having a nevus with risk factors for malignant transformation all developed visible tumors. Notably, cells treated with EVs from UM cell lines (n = 5) also gave rise to tumors in injected mice, suggesting that transforming factors are derived from cancer cells. These data show that cancer-derived EVs harbor signaling factors that, once delivered to target cells, are capable to complete the cascade of events that lead to malignant transformation
Sensing circulating tumorigenic factors will help in the monitoring and early diagnosis of UM patients at risk of metastatic disease. We believe that these data may guide the development of new therapeutic strategies targeting tumorigenic circulating factors, with the ultimate goal of inhibiting the metastatic process in its earliest stages
This is a 2020 ARVO Annual Meeting abstract.
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