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分泌型窖蛋白-1对尤文肉瘤细胞增殖的自刺激作用。

Auto-stimulatory action of secreted caveolin-1 on the proliferation of Ewing's sarcoma cells.

机构信息

Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.

出版信息

Int J Oncol. 2011 May;38(5):1259-65. doi: 10.3892/ijo.2011.963. Epub 2011 Mar 3.

DOI:10.3892/ijo.2011.963
PMID:21373757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3335731/
Abstract

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.

摘要

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。

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本文引用的文献

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Caveolin-1 modulates the ability of Ewing's sarcoma to metastasize.窖蛋白-1调节尤因肉瘤转移的能力。
Mol Cancer Res. 2010 Nov;8(11):1489-500. doi: 10.1158/1541-7786.MCR-10-0060.
2
Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing's sarcoma.致癌伙伴关系:EWS-FLI1 蛋白相互作用引发尤文肉瘤的关键途径。
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Functional analysis of secreted caveolin-1 in mouse models of prostate cancer progression.在前列腺癌进展的小鼠模型中对分泌型窖蛋白-1 的功能分析。
Mol Cancer Res. 2009 Sep;7(9):1446-55. doi: 10.1158/1541-7786.MCR-09-0071. Epub 2009 Sep 8.
5
Caveolin-1 promotes resistance to chemotherapy-induced apoptosis in Ewing's sarcoma cells by modulating PKCalpha phosphorylation.窖蛋白-1 通过调节 PKCalpha 磷酸化促进尤文肉瘤细胞对化疗诱导的细胞凋亡的抵抗。
Int J Cancer. 2010 Jan 15;126(2):426-36. doi: 10.1002/ijc.24754.
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Caveolin-1 tumor-promoting role in human melanoma.小窝蛋白-1在人类黑色素瘤中的促肿瘤作用。
Int J Cancer. 2009 Oct 1;125(7):1514-22. doi: 10.1002/ijc.24451.
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PLoS One. 2009;4(4):e5219. doi: 10.1371/journal.pone.0005219. Epub 2009 Apr 17.
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Childhood and adolescent cancer survival in the US by race and ethnicity for the diagnostic period 1975-1999.1975年至1999年诊断期内美国按种族和族裔划分的儿童及青少年癌症生存率。
Cancer. 2008 Nov 1;113(9):2575-96. doi: 10.1002/cncr.23866.
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Tumor cell-secreted caveolin-1 has proangiogenic activities in prostate cancer.肿瘤细胞分泌的小窝蛋白-1在前列腺癌中具有促血管生成活性。
Cancer Res. 2008 Feb 1;68(3):731-9. doi: 10.1158/0008-5472.CAN-07-2668.
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Caveolin-1 secreting LNCaP cells induce tumor growth of caveolin-1 negative LNCaP cells in vivo.分泌小窝蛋白-1的LNCaP细胞在体内诱导小窝蛋白-1阴性LNCaP细胞的肿瘤生长。
Int J Cancer. 2008 Feb 1;122(3):520-5. doi: 10.1002/ijc.23142.