Cassoni Paola, Senetta Rebecca, Castellano Isabella, Ortolan Erika, Bosco Martino, Magnani Ivana, Ducati Alessandro
Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy.
Am J Surg Pathol. 2007 May;31(5):760-9. doi: 10.1097/01.pas.0000213433.14740.5d.
Caveolins are basic constituents of flask-shaped cell membrane microdomains (caveolae), which are involved in many cell functions, including signalling, trafficking, and cellular growth control. The distribution of caveolae within the normal brain and in brain tumors is controversial. In the present study, we describe the expression of caveolin-1 (cav-1) in 64 brain tumors of different grade, of either astroglial or oligodendroglial origin. All studied astrocitomas of any grade (from II to IV) were cav-1 positive, displaying staining patterns and intensity specifically associated to the different tumor grades. In all glioblastomas and gliosarcomas, cav-1 staining was extremely intense, typically localized at the cell membrane and recognized a variable percentage of cells, including the majority of spindle cells and palisade-oriented perinecrotic cells. In anaplastic astrocytomas, a less intense membrane staining or a cytoplasmic dotlike immunoreactivity were present, the latter being almost the exclusive pattern observed in diffuse astrocitomas grade II. In contrast to astroglial tumors, the striking totality of grade II oligodendrogliomas and the large majority of grade III were lacking cav-1 expression. Interestingly, a cav-1 distribution overlapping the pattern described in tissues was observed also in primary cell cultures of human glioblastomas and astrocytomas, and also in one established glioblastoma cell line (U251 MG), analyzed by means of confocal microscopy and flow cytometry. In conclusion, among astroglial tumors cav-1 expression varies in distribution, pattern, and intensity specifically according to tumor types and grades. The association between tumor progression and a more structured membranous pattern of cav-1 expression could suggest the hypothesis of a neoplastic shift towards a mesenchymal phenotype, whose behavioral and biologic significance worth further studies. Finally, the lack of cav-1 immunoreactivity in oligodendrogliomas suggests its concrete application as a useful diagnostic marker.
小窝蛋白是烧瓶状细胞膜微区（小窝）的基本组成成分，这些微区参与多种细胞功能，包括信号传导、运输和细胞生长控制。小窝在正常脑和脑肿瘤中的分布存在争议。在本研究中，我们描述了小窝蛋白-1（cav-1）在64例不同级别、星形胶质细胞或少突胶质细胞起源的脑肿瘤中的表达情况。所有研究的各级别（从II级到IV级）星形细胞瘤均为cav-1阳性，显示出与不同肿瘤级别特异性相关的染色模式和强度。在所有胶质母细胞瘤和胶质肉瘤中，cav-1染色极其强烈，通常定位于细胞膜，且识别出不同比例的细胞，包括大多数梭形细胞和栅栏状排列的坏死周围细胞。在间变性星形细胞瘤中，存在较弱的细胞膜染色或细胞质点状免疫反应性，后者几乎是II级弥漫性星形细胞瘤中观察到的唯一模式。与星形胶质细胞瘤相反，II级少突胶质细胞瘤几乎全部以及大多数III级少突胶质细胞瘤均缺乏cav-1表达。有趣的是，通过共聚焦显微镜和流式细胞术分析，在人胶质母细胞瘤和星形细胞瘤的原代细胞培养物以及一种已建立的胶质母细胞瘤细胞系（U251 MG）中也观察到了与组织中描述的模式重叠的cav-1分布。总之，在星形胶质细胞瘤中，cav-1表达在分布、模式和强度上根据肿瘤类型和级别而有特异性变化。肿瘤进展与cav-1表达更结构化的膜模式之间的关联可能提示向间充质表型的肿瘤转变这一假说，其行为和生物学意义值得进一步研究。最后，少突胶质细胞瘤中缺乏cav-1免疫反应性表明其可作为一种有用的诊断标志物实际应用。
