Caveolin-1, caveolin-2 and Cavin-1 are strong predictors of adipogenic differentiation in human tumors and cell lines of liposarcoma
Caveolin-1, caveolin-2 and Cavin-1 are strong predictors of adipogenic differentiation in human tumors and cell lines of liposarcoma
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DOI：
10.1016/j.ejcb.2016.04.005
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发表时间：
2016-08-01
影响因子：
6.6
通讯作者：
Fanzani, Alessandro
中科院分区：
文献类型：
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作者：
Codenotti, Silvia;Vezzoli, Marika;Fanzani, Alessandro
Caveolins(Cav-1、-2和-3)和Cavin(Cavin-1、-2、-3和-4)是控制Caveolae生物发生和功能的两个蛋白质家族，质膜上类似omega的内陷代表着重要细胞过程的主要部位，如内吞作用、胆固醇稳态和信号转导。小窝在脂肪组织中尤其丰富，在许多过程中发挥着一致的作用，如胰岛素依赖的葡萄糖摄取和脂肪细胞分化、维持和适应性肥大的脂类跨膜运输。基于这一前提，在这项工作中，我们研究了脂肪肉瘤中空泡蛋白成分的表达。脂肪肉瘤是一种脂肪细胞软组织肉瘤，影响成人，分为高分化型、去分化型、粘液型和多形型。通过对人脂多糖肿瘤进行广泛的基因芯片数据分析和免疫组织化学分析，我们发现Cav-1、Cav-2和Cavin-1总是聚集在所有组织类型中，在分化较好的脂多糖中表达最高，这是由形态类似成熟脂肪细胞的肿瘤细胞组成的最低侵袭性的恶性形式。用两个人内毒素细胞系进行的体外实验表明，在细胞生长过程中，Cav-1、Cav-2和Cavin-1蛋白的表达水平很微弱，随着表征成脂分化的细胞内脂滴的积累，Cav-1、Cav-2和Cavin-1蛋白的表达水平持续上升。此外，免疫荧光和免疫沉淀分析表明，在分化的内毒素细胞中，这三种蛋白在质膜上共定位并形成分子聚集体。总之，这些数据表明Cav-1、Cav-2和Cavin-1可能被认为是鉴定具有一致成脂分化特征的脂多糖肿瘤的可靠标记物。(C)2016年爱思唯尔股份有限公司。版权所有。
Caveolins (Cav-1, -2 and -3) and Cavins (Cavin-1, -2, -3 and -4) are two protein families controlling the biogenesis and function of caveolae, plasma membrane omega-like invaginations representing the primary site of important cellular processes like endocytosis, cholesterol homeostasis and signal transduction. Caveolae are especially abundant in fat tissue, playing a consistent role in a number of processes, such as the insulin-dependent glucose uptake and transmembrane transport of lipids underlying differentiation, maintenance and adaptive hypertrophy of adipocytes. Based on this premise, in this work we have investigated the expression of caveolar protein components in liposarcoma (LPS), an adipocytic soft tissue sarcoma affecting adults categorized in well-differentiated, dedifferentiated, myxoid and pleomorphic histotypes. By performing an extensive microarray data analysis followed by immunohistochemistry on human LPS tumors, we demonstrated that Cav-1, Cav-2 and Cavin-1 always cluster in all the histotypes, reaching the highest expression in well-differentiated LPS, the least aggressive of the malignant forms composed by tumor cells with a morphology resembling mature adipocytes. In vitro experiments carried out using two human LPS cell lines showed that the expression levels of Cav-1, Cav-2 and Cavin-1 proteins were faintly detectable during cell growth, becoming consistently increased during the accumulation of intracellular lipid droplets characterizing the adipogenic differentiation. Moreover, in differentiated LPS cells the three proteins were also found to co-localize and form molecular aggregates at the plasma membrane, as shown via immunofluorescence and immunoprecipitation analysis. Overall, these data indicate that Cav-1, Cav-2 and Cavin-1 may be considered as reliable markers for identification of LPS tumors characterized by consistent adipogenic differentiation. (C) 2016 Elsevier GmbH. All rights reserved.