Gromov Pavel, Celis Julio E, Gromova Irina, Rank Fritz, Timmermans-Wielenga Vera, Moreira José M A
Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Mol Oncol. 2008 Dec;2(4):368-79. doi: 10.1016/j.molonc.2008.09.003. Epub 2008 Oct 2.
Cancer, being a major healthcare concern worldwide, is one of the main targets for the application of emerging proteomic technologies and these tools promise to revolutionize the way cancer will be diagnosed and treated in the near future. Today, as a result of the unprecedented advances that have taken place in molecular biology, cell biology and genomics there is a pressing need to accelerate the translation of basic discoveries into clinical applications. This need, compounded by mounting evidence that cellular model systems are unable to fully recapitulate all biological aspects of human dissease, is driving scientists to increasingly use clinically relevant samples for biomarker and target discovery. Tissues are heterogeneous and as a result optimization of sample preparation is critical for generating accurate, representative, and highly reproducible quantitative data. Although a large number of protocols for preparation of tissue lysates has been published, so far no single recipe is able to provide a "one-size fits all" solubilization procedure that can be used to analyse the same lysate using different proteomics technologies. Here we present evidence showing that cell lysis buffer 1 (CLB1), a lysis solution commercialized by Zeptosens [a division of Bayer (Schweiz) AG], provides excellent sample solubilization and very high 2D PAGE protein resolution both when using carrier ampholytes and immobilized pH gradient strips. Moreover, this buffer can also be used for array-based proteomics (reverse-phase lysate arrays or direct antibody arrays), allowing the direct comparison of qualitative and quantitative data yielded by these technologies when applied to the same samples. The usefulness of the CLB1 solution for gel-based proteomics was further established by 2D PAGE analysis of a number of technically demanding specimens such as breast carcinoma core needle biopsies and problematic tissues such as brain cortex, cerebellum, skeletal muscle, kidney cortex and tongue. This solution when combined with a specific sample preparation technique - cryostat sectioning of frozen specimens - simplifies tissue sample preparation and solves most of the difficulties associated with the integration of data generated by different proteomic technologies.
癌症是全球主要的医疗健康问题之一,是新兴蛋白质组学技术应用的主要目标之一,这些工具有望在不久的将来彻底改变癌症的诊断和治疗方式。如今,由于分子生物学、细胞生物学和基因组学取得了前所未有的进展,迫切需要加快将基础研究成果转化为临床应用。这种需求,再加上越来越多的证据表明细胞模型系统无法完全重现人类疾病的所有生物学方面,促使科学家越来越多地使用临床相关样本进行生物标志物和靶点发现。组织是异质性的,因此优化样本制备对于生成准确、有代表性且高度可重复的定量数据至关重要。尽管已经发表了大量制备组织裂解物的方案,但到目前为止,还没有一种单一的方法能够提供一种“一刀切”的溶解程序,可用于使用不同的蛋白质组学技术分析相同的裂解物。在这里,我们提供证据表明,细胞裂解缓冲液1(CLB1),一种由Zeptosens[拜耳(瑞士)股份公司的一个部门]商业化的裂解溶液,在使用载体两性电解质和固定化pH梯度条时,都能提供出色的样本溶解和非常高的二维聚丙烯酰胺凝胶电泳蛋白质分辨率。此外,这种缓冲液还可用于基于阵列的蛋白质组学(反相裂解物阵列或直接抗体阵列),允许在将这些技术应用于相同样本时直接比较它们产生的定性和定量数据。通过对一些技术要求较高的标本(如乳腺癌粗针活检)以及有问题的组织(如大脑皮层、小脑、骨骼肌、肾皮质和舌头)进行二维聚丙烯酰胺凝胶电泳分析,进一步证实了CLB1溶液在基于凝胶的蛋白质组学中的实用性。当这种溶液与一种特定的样本制备技术——冷冻标本的低温恒温器切片相结合时,简化了组织样本制备,并解决了与整合不同蛋白质组学技术产生的数据相关的大多数困难。