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.

中文翻译：

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Caveolin-1，Caveolin-2和Cavin-1是人类肿瘤和脂肪肉瘤细胞系中成脂分化的重要预测因子。

小窝蛋白（Cav-1，-2和-3）和小孔蛋白（Cavin-1，-2，-3和-4）是两个蛋白家族，它们控制小窝的生物发生和功能，代表主要部位的质膜类似Ω的内陷重要的细胞过程，如胞吞作用，胆固醇稳态和信号转导。小窝在脂肪组织中尤其丰富，在许多过程中起着一致的作用，例如依赖胰岛素​​的葡萄糖摄取和脂质的跨膜转运，这些脂肪是脂肪细胞分化，维持和适应性肥大的基础。基于此前提，在这项工作中，我们研究了脂肪细胞肉瘤（LPS）中的小窝蛋白成分的表达，脂肪肉瘤是影响成人的脂肪细胞软组织肉瘤，分为高分化，去分化，粘液状和多形性组织型。通过对人类LPS肿瘤进行广泛的微阵列数据分析，然后进行免疫组化，我们证明了Cav-1，Cav-2和Cavin-1始终聚集在所有组织型中，在分化良好的LPS中表达最高，而对LPS侵袭性最低由具有类似于成熟脂肪细胞形态的肿瘤细胞组成的恶性形式。使用两种人LPS细胞系进行的体外实验表明，在细胞生长过程中微弱地检测到Cav-1，Cav-2和Cavin-1蛋白的表达水平，在表征成脂分化的细胞内脂质小滴蓄积期间不断增加。此外，在分化的LPS细胞中，还发现这三种蛋白质在质膜上共定位并形成分子聚集体，如通过免疫荧光和免疫沉淀分析所示。总体而言，这些数据表明，Cav-1，Cav-2和Cavin-1可能被视为鉴定以一致的成脂分化为特征的LPS肿瘤的可靠标记。