Autophagy and vesicular trafficking in human uveal melanoma: A histopathological study

Abstract

Uveal melanoma is an ocular tumor with a high risk of developing metastases. The endo‐lysosomal system can affect the melanoma progression by accelerating and facilitating invasion or metastasis. This study aims to conduct comparative analysis of normal choroidal melanocytes and uveal melanoma cells ultrastructure with a focus on intracellular transport system, and to examine the patterns of autophagy‐ and vesicular trafficking‐related proteins expression in a case series of uveal melanomas. Transmission electron microscopy was used to assess the ultrastructure of normal choroidal melanocytes and uveal melanoma cells. The expression levels of autophagy‐ and vesicular trafficking‐related proteins in three histological types of uveal melanoma were analyzed by immunofluorescence staining. Electron microscopy results showed that the autophagic vacuoles were more abundant in normal choroidal melanocytes, than in uveal melanoma cells. The normal choroidal melanocytes were characterized by active intracellular vesicular trafficking; however, the proportion of caveolae was higher in uveal melanoma cells. The spindle type of tumor was characterized by a high expression levels of LC3 beta, while Rab7 and Rab11 proteins expression was significantly up‐regulated in the mixed‐type tumor cells. The results indicate that uveal melanoma cells probably have lower basal levels of autophagy and higher receptor‐mediated endocytic trafficking‐associated with caveolae than normal choroidal melanocytes.Research Highlights The autophagic vacuoles are abundant in normal choroidal melanocytes. Uveal melanoma cells are characterized by a high proportion of caveolae. The high expression levels of LC3 beta were revealed in a spindle type of tumor, while Rab7 and Rab11 proteins expression was up‐regulated in the mixed‐type tumor cells.

Current and Emerging Radiotherapy Options for Uveal Melanoma

“…These genes encode proteins involved in the RAS-RAF-MEK-ERK- (MAPK) pathway which is critical to cell growth and proliferation [ 8 ]. Dysregulation of other cellular pathways autophagy has also been implicated in uveal melanoma tumorigenesis [ 9 ]. Cytogenetic rearrangements in uveal melanoma most commonly affect chromosomes 1, 3, 6, and 8 and can predict the risk of poor outcomes.…”

“…SF3B1 mutations which affect spliceosomes are more often found in younger patients and seem to carry an intermediate risk of metastasis which can develop several years after diagnosis. The various molecular mechanisms of tumorigenesis and the development of metastatic potential are attractive targets for a range of systemic therapies and remain under active investigation [ 8 , 9 ].…”