Validated Modeling and Culture of Salivary Cancers

描述（由申请人提供）：涎腺癌是一组毁灭性的恶性肿瘤，几乎完全通过手术切除伴或不伴放射治疗。低发病率，多种组织学，缺乏分子细节和收集这些肿瘤的基础设施不足，都导致了治疗选择的相对缺乏。我们认为，最大的障碍，阻碍了解唾液腺癌和治疗的进步一直是缺乏或缺乏有效的异种移植模型或细胞系的研究。如果没有可自由获得的异种移植物或细胞系，则不可能进行机理或临床前研究。在这里，我们建议建立小鼠异种移植模型的人类涎腺癌的多种组织学。我们有异种移植的多种唾液腺类型，包括：腺样囊性癌，腺癌未另行说明，多形性低级别腺癌，癌外多形性腺瘤，和唾液腺导管癌。我们还建议使用原发性肿瘤或小鼠异种移植肿瘤作为起始材料，从多种组织学类型的唾液腺癌中创建细胞系。对于细胞系的开发，我们继续通过调整肿瘤解离方案、培养基、平板包被和培养缺氧来优化我们的培养环境。通过进行这些调整，我们增加了来自多种唾液腺癌类型的早期细胞培养的成功率，并且我们目前拥有来自腺癌（未另行说明）、多形性低级别腺癌和癌外多形性腺瘤的细胞的活跃早期传代。一旦建立异种移植物和细胞系，将通过比较形态学（异种移植物）和基因表达（异种移植物和细胞培养物）对其进行验证。我们拥有从手术切除中收集唾液腺癌的基础设施，并在短期培养和小鼠异种移植模型的肿瘤处理方面积累了专业知识。我们将利用这些资源来创建和验证唾液腺癌的小鼠异种移植模型和细胞系。这些经过验证的细胞系和异种移植肿瘤对于促进唾液腺癌的分子理解至关重要，并且对于治疗的进步也是必需的。

DESCRIPTION (provided by applicant): Salivary cancers are a devastating group of malignancies treated almost exclusively by surgical excision with or without radiation. The low incidences, multiple histologies, lack of molecular details and inadequate infrastructure for collecting these tumors have each contributed to the relative paucity of treatment options. We suggest that the largest impediment blocking understanding of salivary cancers and advancement of therapy has been the lack or scarcity of validated xenograft models or cell lines for study. Without freely available xenografts or cell lines mechanistic or pre-clinical studies ar not possible. Here, we propose to create mouse xenograft models of human salivary cancers of multiple histologies. We have xenografted multiple salivary types including: adenoid cystic, adenocarcinoma not otherwise specified, polymorphous low grade adenocarcinoma, carcinoma ex-pleomorphic adenoma, and salivary ductal carcinoma. We also propose to create cell lines from multiple histological types of salivary cancer using primary tumors or murine xenografted tumors as starting material. For development of cell lines, we continue to optimize our culture environment with adjustment of tumor dissociation protocols, media, plate coatings, and culture hypoxia. By making these adjustments, we have increased our success of early cell culture derived from multiple salivary cancer types, and we currently have active early passages of cells derived from adenocarcinoma not otherwise specified, polymorphous low grade adenocarcinoma, and carcinoma ex-pleomorphic adenoma. Once xenografts and cell lines are created, they will be validated by comparison of morphology (xenografts) and gene expression (xenografts and cell cultures). We have the infrastructure for collection of salivary cancers from surgical resections and have developed expertise in processing of the tumors for short-term culture and murine xenograft modeling. We will leverage these resources to create and validate murine xenograft models and cell lines for salivary cancers. These validated cell lines and xenografted tumors will be critical to advance molecular understanding of salivary cancers and will be needed for advancement of therapy.