Kuick Rork, Misek David E, Monsma David J, Webb Craig P, Wang Hong, Peterson Kelli J, Pisano Michael, Omenn Gilbert S, Hanash Samir M
Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, MI, USA.
Cancer Lett. 2007 Apr 28;249(1):40-8. doi: 10.1016/j.canlet.2006.12.032. Epub 2007 Feb 22.
Although our understanding of the molecular pathogenesis of common types of cancer has improved considerably, the development of effective strategies for cancer diagnosis and treatment have lagged behind. Mouse models of cancer potentially represent an efficient means for uncovering diagnostic markers as genetic alterations associated with human tumors can be engineered in mice. In addition, defined stages of tumor development, breeding conditions, and blood sampling can all be controlled and standardized to limit heterogeneity. Alternatively human cancer cells can be injected into mice and tumor development monitored in xenotransplants. Mouse-based studies promise to elucidate a repertoire of protein changes that occur in blood and biological fluids during tumor development. This is illustrated in a study in which we have applied a three-dimensional intact protein analysis system (IPAS) to elucidate detectable protein changes in serum from immunodeficient mice with lung xenografts from orthotopically implanted human A549 lung adenocarcinoma cells. With sufficiently detailed protein sequence identifications, the observed protein changes can be attributed to either the host mouse or the human tumor cells. It is noteworthy that the majority of increases identified have corresponded to relatively abundant serum proteins, some of which have previously been reported as increased in the sera of cancer patients. Proteomic studies of mouse models of cancer allow assessment of the range of changes in plasma proteins that occur with tumor development and may lead to the identification of potential cancer markers applicable to humans.
尽管我们对常见类型癌症的分子发病机制已有相当程度的了解，但癌症诊断和治疗有效策略的开发却滞后了。癌症小鼠模型可能是一种揭示诊断标志物的有效手段，因为与人类肿瘤相关的基因改变可以在小鼠中进行构建。此外，肿瘤发展的特定阶段、繁殖条件和血液采样都可以得到控制和标准化，以限制异质性。或者，可以将人类癌细胞注射到小鼠体内，并在异种移植中监测肿瘤的发展。基于小鼠的研究有望阐明肿瘤发展过程中血液和生物体液中发生的一系列蛋白质变化。这在一项研究中得到了体现，在该研究中，我们应用了三维完整蛋白质分析系统（IPAS）来阐明来自原位植入人A549肺腺癌细胞的肺异种移植免疫缺陷小鼠血清中可检测到的蛋白质变化。通过足够详细的蛋白质序列鉴定，观察到的蛋白质变化可以归因于宿主小鼠或人类肿瘤细胞。值得注意的是，鉴定出的大多数增加都对应于相对丰富的血清蛋白，其中一些先前已报道在癌症患者血清中增加。癌症小鼠模型的蛋白质组学研究可以评估肿瘤发展过程中血浆蛋白发生的变化范围，并可能导致鉴定出适用于人类的潜在癌症标志物。
