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）转化科学和特定的挑战主题，15-DE-101唾液腺肿瘤研究的分子特征分析和小鼠模型开发。拟议的工作将扩大一个正在进行的成功的研究计划，在免疫缺陷小鼠中建立人类唾液腺腺样囊性癌肿瘤异种移植物，以包括其他常见的和临床上具有侵袭性的人类唾液腺肿瘤类型。研究者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登记处的资源，收集用于异种移植物植入的活肿瘤样本。将在基因组和蛋白质组水平上表征所得异种移植物（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公开网站上提供。将特别强调创建一个股票的活冷冻组织和创建组织样本的组织微阵列模型，从而创建虚拟的和真实的唾液腺肿瘤资源，研究人员可以查询创建假设的唾液腺肿瘤生物学，并要求材料来测试这些假设。这些异种移植模型系统的使用包括提供用于发现科学的原材料、衍生细胞培养系的来源、用于体内测试与唾液腺肿瘤生物学相关的假设的试剂和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：人类唾液腺肿瘤的研究受到缺乏模型系统和肿瘤组织研究的阻碍。我们建议在小鼠中连续生长从患者获得的唾液腺肿瘤，其可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.