Taskaeva Iuliia, Shatruk Anastasia, Bgatova Nataliya, Yeremina Alena, Trunov Aleksander, Kononova Natalya, Chernykh Valeriy
Laboratory of Ultrastructural Research, Research Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
S. N. Fyodorov Federal State Institution National Medical Research Center Intersectoral Research and Technology Complex "Eye Microsurgery" Ministry of Health of the Russian Federation, Novosibirsk, Russia.
Microsc Res Tech. 2024 Jan;87(1):122-132. doi: 10.1002/jemt.24417. Epub 2023 Sep 12.
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.
葡萄膜黑色素瘤是一种具有高转移风险的眼部肿瘤。内溶酶体系统可通过加速和促进侵袭或转移来影响黑色素瘤的进展。本研究旨在对正常脉络膜黑色素细胞和葡萄膜黑色素瘤细胞的超微结构进行比较分析，重点关注细胞内运输系统，并在一系列葡萄膜黑色素瘤病例中检测自噬和囊泡运输相关蛋白的表达模式。采用透射电子显微镜评估正常脉络膜黑色素细胞和葡萄膜黑色素瘤细胞的超微结构。通过免疫荧光染色分析三种组织学类型的葡萄膜黑色素瘤中自噬和囊泡运输相关蛋白的表达水平。电子显微镜结果显示，正常脉络膜黑色素细胞中的自噬空泡比葡萄膜黑色素瘤细胞中更丰富。正常脉络膜黑色素细胞的特征是细胞内囊泡运输活跃；然而，葡萄膜黑色素瘤细胞中的小窝比例更高。纺锤形肿瘤的特征是LC3β表达水平高，而Rab7和Rab11蛋白在混合型肿瘤细胞中的表达显著上调。结果表明，与正常脉络膜黑色素细胞相比，葡萄膜黑色素瘤细胞的基础自噬水平可能较低，且与小窝相关的受体介导的内吞运输较高。研究亮点：正常脉络膜黑色素细胞中自噬空泡丰富。葡萄膜黑色素瘤细胞的特征是小窝比例高。在纺锤形肿瘤中发现LC3β表达水平高，而Rab7和Rab11蛋白在混合型肿瘤细胞中的表达上调。
