Molecular characterization of a human salivary gland tumor xenograft bank

描述(由申请人提供)：本申请涉及广泛的挑战领域(15)翻译科学和特定的挑战主题，15-DE-101分子图谱和发展唾液腺肿瘤研究的小鼠模型。这项拟议的工作将扩大正在进行的在免疫缺陷小鼠中创建人涎腺腺样囊性癌异种移植瘤的成功研究计划，以包括其他常见和临床侵袭性的人类唾液腺肿瘤类型。研究人员将利用弗吉尼亚大学生物库、密歇根大学组织采购机构、NIDCR赞助的唾液腺肿瘤生物库、NCI赞助的合作人类组织网络和腺样囊性癌注册中心的资源来收集可用于异种移植的肿瘤样本。由此产生的异种移植将在基因组和蛋白质水平上进行表征(细胞遗传学、阵列CGH、微阵列基因表达谱、蛋白质磷酸化的质谱分析)。这些分析的原始数据将在一个公开的网站上公布。将特别强调创建可见的冰冻组织库存，并根据模型创建组织样本的组织微阵列，从而创建虚拟和真实的唾液腺肿瘤资源，研究人员可以查询这些资源来创建唾液腺肿瘤生物学假说，并请求材料来验证这些假说。这些异种移植模型系统的使用包括为发现科学提供原料，提供细胞培养系的来源，用于体内验证与唾液腺肿瘤生物学相关的假说的试剂，以及用于这些肿瘤类型的治疗策略的临床前测试的试剂。 公共卫生相关性：由于缺乏可供研究的模型系统和肿瘤组织，人类唾液腺肿瘤的研究受到阻碍。我们建议在小鼠体内持续生长从患者身上获得的唾液腺肿瘤，这些肿瘤可以用于实验，以了解这些肿瘤的分子基础，并测试新的治疗形式。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DE-101 Molecular Profiling and Developing Mouse Models for Salivary Gland Tumor Research. The proposed work will expand an ongoing successful research program of creating human salivary adenoid cystic carcinoma tumor xenografts in immunodeficient mice to include the other common and clinically aggressive human salivary gland tumor types. The investigators will utilize the resources of the University of Virginia Biorepository, the University of Michigan Tissue Procurement Facility, the NIDCR-sponsored Salivary Gland Tumor Biorepository, the NCI-sponsored Cooperative Human Tissue Network and the Adenoid Cystic Carcinoma Registry to collect viable tumor samples for xenograft implantation. Resulting xenografts will be characterized on the genomic and proteomic level (cytogenetics, array CGH, microarray gene expression profiling, mass spectroscopic analysis of protein phosphorylation). The raw data from these analyses will be made available on a publicly-available website. Special emphasis will be given to creating a stock of viably frozen tissue and creating tissue microarrays of tissue samples from the model, thus creating virtual and real salivary gland tumor resources that investigators may query to create hypotheses of salivary gland tumor biology, and request materials to test those hypotheses. The use of these xenograft model systems include providing raw material for discovery science, a source to derive cell culture lines, reagents for in vivo testing of hypotheses related to salivary gland tumor biology and reagents for preclinical testing of therapeutic strategies for these tumor types. PUBLIC HEALTH RELEVANCE: The study of human salivary gland tumors is hampered by a lack of model systems and tumor tissue to study. We propose to continuously grow salivary gland tumors obtained from patients in mice, which can be used in experiments to understand the molecular basis of these tumors and to test new forms of therapy.