人类虹膜黑素瘤中的自噬和囊泡运输: 一项组织病理学研究。
Autophagy and vesicular trafficking in human uveal melanoma: A histopathological study.
发表日期:2023 Sep 12
作者:
Iuliia Taskaeva, Anastasia Shatruk, Nataliya Bgatova, Alena Yeremina, Aleksander Trunov, Natalya Kononova, Valeriy Chernykh
来源:
MICROSCOPY RESEARCH AND TECHNIQUE
摘要:
葡萄膜黑色素瘤是一种眼部肿瘤,具有发生转移的高风险。内源性溶酶体系统可以通过加速和促进肿瘤的侵袭或转移来影响黑色素瘤的进展。本研究旨在比较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,重点研究细胞内运输系统,并检测一系列葡萄膜黑色素瘤病例中与自噬和囊泡运输相关的蛋白质表达模式。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了三种组织学类型的葡萄膜黑色素瘤中与自噬和囊泡运输相关的蛋白质的表达水平。电子显微镜结果显示,自噬液泡在正常脉络膜黑色素细胞中较丰富,而在葡萄膜黑色素瘤细胞中较少。正常脉络膜黑色素细胞具有活跃的细胞内囊泡运输,然而葡萄膜黑色素瘤细胞中小窝的比例更高。梭形瘤型表现出较高水平的LC3β蛋白表达,而混合型肿瘤细胞中Rab7和Rab11蛋白的表达显著上调。研究结果表明,与正常脉络膜黑色素细胞相比,葡萄膜黑色素瘤细胞可能具有较低的自噬基础水平和较高的与小窝相关的受体介导的内吞作用。研究亮点:正常脉络膜黑色素细胞中存在丰富的自噬液泡。葡萄膜黑色素瘤细胞的特点是小窝的比例较高。梭形瘤型表现出较高水平的LC3β蛋白表达,而混合型肿瘤细胞中Rab7和Rab11蛋白的表达上调。©2023 Wiley Periodicals LLC.
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.© 2023 Wiley Periodicals LLC.