Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133.

Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133.
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DOI:
10.3390/cancers3032870
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发表时间:
2011-07-13
期刊:
影响因子:
5.2
通讯作者:
Braciak TA
Braciak TA
中科院分区:
医学2区
文献类型:
--
作者:
Steinmetz NF;Maurer J;Sheng H;Bensussan A;Maricic I;Kumar V;Braciak TA

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波形蛋白最初被鉴定为在许多细胞类型中仅作为细胞内组分存在的中间丝蛋白。然而,这种蛋白质现在已经在许多不同的癌细胞类型的表面上以点状分布模式被检测到。波形蛋白表达的增加被认为是前列腺癌转移所需的上皮-间质转化(EMT)的重要步骤。在这里,使用两种波形蛋白特异性单克隆抗体(SC 5和V9分别针对线圈一杆结构域和波形蛋白的C-末端),我们研究了这些结构域中的任何一个是否会显示在从不同转移部位分离的三种常用研究的前列腺癌细胞系的表面上。LNCaP、PC 3和DU 145前列腺癌细胞系(分别源自淋巴结、骨或脑前列腺转移)的共聚焦分析表明,波形蛋白的两个结构域都存在于这些转移性癌细胞类型的表面上。此外,流式细胞术分析显示,波形蛋白表达很容易检测到沿着CD 44表达,但只有一小部分前列腺癌细胞表达波形蛋白和推定的干细胞标记物CD 133沿着CD 44。最后,靶向波形蛋白的豇豆花叶病毒(CPMV)纳米颗粒可以结合并内化到测试的前列腺癌细胞系中。这些结果表明,波形蛋白的至少两个结构域存在于转移性前列腺癌细胞的表面上,并且表明波形蛋白可以为针对高度侵袭性癌症和/或干细胞的纳米颗粒或抗体癌症治疗剂提供有用的靶标。
Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.