A Chemical Proteomics Approach for the Identification of Accessible Antigens Expressed in Human Kidney Cancer*S
A Chemical Proteomics Approach for the Identification of Accessible Antigens Expressed in Human Kidney Cancer*S
复制标题
用于鉴定人肾癌*S中表达的可接近抗原的化学蛋白质组学方法
DOI：
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发表时间：
2006
影响因子：
7
通讯作者：
D. Neri
中科院分区：
文献类型：
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作者：
V. Castronovo;D. Waltregny;P. Kischel;C. Roesli;G. Elia;Jascha;D. Neri
一个有希望的途径，朝着更有选择性的抗癌药物的发展在于靶向递送的生物活性分子的肿瘤环境的方式特异性结合分子的肿瘤相关标志物。我们使用了一种化学蛋白质组学方法，该方法基于手术切除的具有肿瘤的人肾脏内的可接近结构的离体灌注和生物素化，以获得关于在人类癌症中过表达的可接近和丰富的抗原的信息。该过程导致用生物素对血管结构进行选择性标记。生物素化的蛋白质链霉亲和素树脂纯化，并确定使用质谱方法，揭示637种蛋白质，其中184只发现在肿瘤标本和223只发现在部分正常肾脏。免疫组织化学和PCR分析证实，在这项研究中确定的几个假定的癌抗原确实优先在肿瘤中表达。总之，我们已经开发了一种方法，允许在人体组织中识别可访问的生物标志物。本研究中鉴定的肿瘤相关抗原可能是基于抗体的抗癌治疗的合适靶点。这里描述的实验方法应该适用于其他手术标本和其他病理以及基本的生理和免疫过程的研究。
A promising avenue toward the development of more selective anticancer drugs consists in the targeted delivery of bioactive molecules to the tumor environment by means of binding molecules specific to tumor-associated markers. We have used a chemical proteomics approach based on the ex vivo perfusion and biotinylation of accessible structures within surgically resected human kidneys with tumor to gain information about accessible and abundant antigens that are overexpressed in human cancer. This procedure led to the selective labeling with biotin of vascular structures. Biotinylated proteins were purified on streptavidin resin and identified using mass spectrometric methodologies, revealing 637 proteins, 184 of which were only found in tumor specimens and 223 of which were only found in portions of normal kidneys. Immunohistochemical and PCR analysis confirmed that several of the putative cancer antigens identified in this study are indeed preferentially expressed in tumors. In conclusion, we have developed a methodology that allows the identification of accessible biomarkers in human tissues. The tumor-associated antigens identified in this study may be suitable targets for antibody-based anticancer therapies. The experimental approach described here should be applicable to other surgical specimens and to other pathologies as well as to the study of basic physiological and immunological processes.
影响因子：
56.9
作者：
Arap, W;Pasqualini, R;Ruoslahti, E
通讯作者：
Ruoslahti, E