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A Novel Truncated Form of Nephronectin Is Present in Small Extracellular Vesicles Isolated from 66cl4 Cells.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2019-02-13 , DOI: 10.1021/acs.jproteome.8b00859 Jimita Toraskar 1 , Synnøve N Magnussen 2 , Lars Hagen 1, 3 , Animesh Sharma 3 , Linh Hoang , Geir Bjørkøy , Gunbjørg Svineng 2 , Tonje S Steigedal 1
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2019-02-13 , DOI: 10.1021/acs.jproteome.8b00859 Jimita Toraskar 1 , Synnøve N Magnussen 2 , Lars Hagen 1, 3 , Animesh Sharma 3 , Linh Hoang , Geir Bjørkøy , Gunbjørg Svineng 2 , Tonje S Steigedal 1
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Extracellular vesicles are emerging as biomarkers in breast cancer. Our recent report suggested that an intracellular granular staining pattern of the extracellular matrix protein nephronectin (NPNT) in breast tumor sections correlated with a poor prognosis. Furthermore, the results showed that NPNT is localized in extracellular vesicles derived from mouse breast cancer cells. In this study, we performed proteomic analysis that revealed that several proteins, including tumor-promoting molecules, are differentially expressed in the cargo of small extracellular vesicles (sEVs) derived from NPNT-expressing mouse breast cancer cells. We also identified three different forms of NPNT at 80, 60, and 20 kDa. We report that the native form of NPNT at 60 kDa becomes further glycosylated and is detected as the 80 kDa NPNT, which may be processed by matrix metalloproteinases to a shorter form of around 20 kDa, which has not previously been described. Although both 80 and 20 kDa NPNT are detected in sEVs derived from breast cancer cells, the 20 kDa form of NPNT is concentrated in sEVs. In summary, we show that a novel truncated form of NPNT is found in sEVs derived from breast cancer cells.
中文翻译：
Nephronectin的新型截短形式存在于从66cl4细胞分离的小细胞外囊泡中。
细胞外囊泡正在作为乳腺癌的生物标志物出现。我们的最新报告表明，乳腺肿瘤切片中胞外基质蛋白肾粘连蛋白（NPNT）的胞内颗粒染色模式与不良预后相关。此外，结果表明，NPNT位于源自小鼠乳腺癌细胞的细胞外囊泡中。在这项研究中，我们进行了蛋白质组学分析，结果表明，几种蛋白质，包括促肿瘤分子，在表达NPNT的小鼠乳腺癌细胞衍生的小细胞外囊泡（sEVs）的货物中差异表达。我们还确定了80、60和20 kDa的NPNT的三种不同形式。我们报告说，在60 kDa的NPNT天然形式变得进一步糖基化，并被检测为80 kDa NPNT，可以通过基质金属蛋白酶将其加工成约20kDa的较短形式，这之前没有描述。尽管在源自乳腺癌细胞的sEV中同时检测到80 kDa和20 kDa NPNT，但20 kDa形式的NPNT却集中在sEV中。总而言之，我们表明在源自乳腺癌细胞的sEV中发现了一种新的截短形式的NPNT。
更新日期：2019-02-14
中文翻译：
Nephronectin的新型截短形式存在于从66cl4细胞分离的小细胞外囊泡中。
细胞外囊泡正在作为乳腺癌的生物标志物出现。我们的最新报告表明，乳腺肿瘤切片中胞外基质蛋白肾粘连蛋白（NPNT）的胞内颗粒染色模式与不良预后相关。此外，结果表明，NPNT位于源自小鼠乳腺癌细胞的细胞外囊泡中。在这项研究中，我们进行了蛋白质组学分析，结果表明，几种蛋白质，包括促肿瘤分子，在表达NPNT的小鼠乳腺癌细胞衍生的小细胞外囊泡（sEVs）的货物中差异表达。我们还确定了80、60和20 kDa的NPNT的三种不同形式。我们报告说，在60 kDa的NPNT天然形式变得进一步糖基化，并被检测为80 kDa NPNT，可以通过基质金属蛋白酶将其加工成约20kDa的较短形式，这之前没有描述。尽管在源自乳腺癌细胞的sEV中同时检测到80 kDa和20 kDa NPNT，但20 kDa形式的NPNT却集中在sEV中。总而言之，我们表明在源自乳腺癌细胞的sEV中发现了一种新的截短形式的NPNT。
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