Development of a Human Intraepithelial Cancer Model

描述(申请人提供)：超过一半的人类癌症发生在 鳞状上皮。为了加强治疗癌症的药物发现 鳞状细胞癌(SCC)和其他癌症，有必要有一个 重现肿瘤和正常上皮的器官型体外模型 互动。艾伦-霍夫曼实验室最近开发出一种器官类型 允许评估分层人体鳞状细胞中肿瘤生长的模型 上皮细胞。该模型是基因标记的人类SCC细胞和 无标记的自然永生化的人类角质形成细胞称为NIKS细胞。 与目前的体外检测不同，该模型考虑了 正常组织微环境对鳞癌生长分化的影响 细胞。另一个优势是该模型与其他上皮性癌症的相关性 (例如，宫颈、气管)及其与其他治疗相结合的能力 (例如，手术、放射治疗)。我们对此提案的策略是验证和 在已知和新颖的情况下优化器官类型共培养 抗癌药物(如化疗药物、细胞抑制药物)和量化 它们通过监测基因标记的鳞癌对恶性细胞生长的影响 细胞。在这项第一阶段工作完成前，我们计划发展一套 高通量、微升容量的筛选格式以识别新的 抗肿瘤药物采用以NIKS为基础的、人NTM肿瘤试验。 建议的商业应用： 体外模型能够测试潜力对于有效药物的发现是至关重要的 与生理相关的抗癌药物。Stratech正在开发产品 以及使用带有基因标记的鳞状细胞癌的共培养系统的服务 (SCC)细胞在由我们的原代NIKS细胞系组成的器官型培养中。这款车 该系统代表了筛选潜在药物或药物的重大技术进步 用于治疗复层鳞状上皮癌(例如，头颈部，口腔粘膜， 宫颈、气管)。

DESCRIPTION (PROVIDED BY APPLICANT): Over half of all human cancers occur in squamous epithelia. In order to enhance drug discovery for the treatment of squamous cell carcinoma (SCC) and other cancers, it is essential to have an organotypic in vitro model which recapitulates tumor and normal epithelial interactions. The Allen-Hoffmann laboratory recently developed an organotypic model that permits the assessment of tumor growth in stratified human squamous epithelia. The model is a co-culture of genetically marked human SCC cells and unmarked spontaneously immortalized human keratinocytes called NIKS cells. Unlike current in vitro assays, this model accounts for the influence of the normal tissue microenvironment (NTM) on the growth and differentiation of SCC cells. Another advantage is the model's relevance for other epithelial cancers (e.g., cervix, trachea) and its capacity for combination with other treatments (e.g., surgery, radiation). Our strategy for this proposal is to validate and optimize the organotypic co-cultures in the presence of known and novel anticancer agents (e.g., chemotherapeutics, cytostatic drugs) and quantify their effect on malignant cell growth by monitoring the genetically marked SCC cells. Pending completion of this Phase I work, we plan to develop a high-throughput, microliter-volume screening format to identify novel anti-tumor agents using the NIKS-based, human NTM tumor assay. PROPOSED COMMERCIAL APPLICATION: It is essential for effective durg discovery that in vitro models be able to test potential anticancer agents in a physiologically relevant context. Stratatech is developing products and services using a co-cultured system of genetically tagged squamous cell carcinoma (SCC) cells in an organotypic culture comprised of our propietary NIKS cell line. This model system represents a major technological advance for screening drugs or agents of potential use in treating cancers of the stratified squamous epithelia (e.g., head and neck, oral mucosa, cervix, trachea).