Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Int J Oncol. 2011 May;38(5):1259-65. doi: 10.3892/ijo.2011.963. Epub 2011 Mar 3.
Caveolin-1 (CAV1) is highly expressed in Ewing's sarcoma (EWS). We previously showed that increased cellular CAV1 is associated with the regulation of the tumorigenicity, drug resistance and metastatic ability of EWS cells. Because several studies reported that melanoma and prostate cancer cells, which express relatively high CAV1 levels, secrete CAV1, and that secreted CAV1 is associated with tumor progression, our study explored the possibility that EWS cells also secreted CAV1 and that secreted CAV1 may contribute to EWS pathobiology. Results from experiments involving the ectopic expression of a Myc-tagged CAV1 protein in EWS cells as well as the supplementation of culture media with purified CAV1 protein followed by its intracellular localization using immunofluorescence demonstrated that EWS cells secrete CAV1, that they are able to take up the secreted protein, and that extracellular CAV1 enhances EWS cell proliferation. These findings strongly support the notion that secreted CAV1 may also contribute to the malignant properties of EWS.
窖蛋白-1(CAV1)在尤因肉瘤(EWS)中高度表达。我们之前的研究表明,细胞内 CAV1 的增加与 EWS 细胞的致瘤性、耐药性和转移能力的调节有关。由于几项研究报道,表达相对较高 CAV1 水平的黑色素瘤和前列腺癌细胞会分泌 CAV1,并且分泌的 CAV1 与肿瘤进展有关,因此我们的研究探讨了 EWS 细胞是否也分泌 CAV1,以及分泌的 CAV1 是否可能有助于 EWS 的病理生物学。通过在 EWS 细胞中外源表达 Myc 标记的 CAV1 蛋白的实验,以及用纯化的 CAV1 蛋白补充培养基,然后用免疫荧光法检测其细胞内定位的实验结果表明,EWS 细胞分泌 CAV1,它们能够摄取分泌的蛋白,并且细胞外 CAV1 增强了 EWS 细胞的增殖。这些发现有力地支持了这样一种观点,即分泌的 CAV1 也可能有助于 EWS 的恶性特性。