Isolation and characterization of the normal and cancer stem cells of the tongue.

舌头正常干细胞和癌症干细胞的分离和表征。

• 批准号: 8032812
• 负责人: Agnieszka Kobielak
• 金额: $ 24.3万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8032812
• 关键词: Accounting; Affect; Age; Blood; Cell Cycle; Cell surface; Cells; Characteristics; Critical Pathways; Data; Detection; Development; Diagnosis; Disease; Distant Metastasis; Epithelium; Future; Gene Expression; Genotype; Goals; Growth; Head and Neck Squamous Cell Carcinoma; Heterogeneity; Human; Incidence; Label; Lateral; Malignant Neoplasms; Methodology; Methods; Molecular; Molecular Profiling; Multi-Drug Resistance; Mus; Neoplasm Metastasis; Neoplasms; Normal tissue morphology; Oral cavity; Oropharyngeal; Outcome; Pathway interactions; Patients; Population; Preparation; Process; Property; Proteins; Recurrence; Regimen; Research; Route; Sampling; Stem cells; Survival Rate; Testing; Therapeutic; Time; Tongue; Tongue Carcinoma; Tongue Neoplasms; Tongue Squamous Cell Carcinoma; United States; anticancer research; base; cancer cell; cancer gene expression; cancer stem cell; cancer therapy; chemotherapy; drug use screening; improved; malignant tongue neoplasm; mortality; mouse model; oral cavity epithelium; self-renewal; slow potential; stem cell population; therapy development; therapy resistant; tongue sampling; treatment strategy; tumor; young adult

DESCRIPTION (provided by applicant): Oral epithelium cancer is a common malignancy that affects 40,000 new patients in the United States each year. Mortality from this disease remains high because of the development of distant metastases and the emergence of therapy-resistant local and regional recurrences. The median age at diagnosis for head and neck squamous cell carcinoma (HNSCC) has classically and historically been set at 60 years. The incidence of a subset of neoplasms originating from the oral cavity and the oropharynx, however, in young adults, age <40, has been steadily and rapidly increasing. Furthermore, carcinoma of the tongue appears to account for the majority of this increase in incidence and has now become the second most common malignancy in the oral cavity. Recent research suggests that tumor formation may result from the development of cancer stem cells. According to this hypothesis tumors harbor a small population of cancer stem cells (CSC) that are responsible for re-growth of a tumor following unsuccessful treatment and for the establishment of metastases. The successful treatment to eliminate cancer need to take into account the unusual properties of the CSC subpopulation. A major problem to the development of such a treatment strategy is that methods are still lacking that can readily distinguish CSCs from their differentiating progeny and from their normal tissue counterparts. Purification of cancer stem cells from human tumors is limited by patient heterogeneity and availability of fresh and sizable tumor samples. Moreover, current markers enrich for but do not allow complete purification of human CSCs. Based on our preliminary observations we propose an alternative route to obtain and characterize oral epithelia normal and cancer stem cells using mouse model. Obtained in our study gene expression profiles of normal tongue epithelium stem cells versus cancer stem cells could be used to identify cell surface or secreted proteins enriched in CSC population, which may be used to guide the identification, further purification, and blood-based detection of human cancer. Experimentally isolated CSC may also be used for drug screening to identify compounds that specifically target cancer stem cells. Further, a key goal in cancer research is to identify the mechanism by which cancer stem cells arise and self- renew. Mouse models with defined CSC offer the possibility of dissecting the temporal and functional dynamics of these processes. PUBLIC HEALTH RELEVANCE: Oral epithelium cancer is a common malignancy with still high mortality rate. Recent studies suggest that tumors harbor a small population of cancer stem cells (CSC) that are responsible for re-growth of a tumor following unsuccessful treatment. To improve the current treatment we need to take into account the unusual properties of the CSC subpopulation. Our overall goal is to isolate and characterize normal and cancer tongue epithelium stem cells and characterize how the tongue epithelium cancer stem cells differ from their differentiating progeny and from normal stem cells. This might allow to target selectively and eliminate CSC, thus improving therapeutic outcome.

描述（由申请人提供）：口腔上皮癌是一种常见的恶性肿瘤，每年影响美国 40,000 名新患者。由于远处转移的发生以及局部和区域性耐药性复发的出现，这种疾病的死亡率仍然很高。头颈鳞状细胞癌 (HNSCC) 诊断的中位年龄传统上和历史上被定为 60 岁。然而，在年龄 <40 岁的年轻人中，起源于口腔和口咽部的肿瘤的发病率一直在稳步快速增加。此外，舌癌似乎是发病率增加的主要原因，现已成为口腔中第二常见的恶性肿瘤。 最近的研究表明，肿瘤的形成可能是癌症干细胞发育的结果。根据这一假设，肿瘤中含有一小群癌症干细胞（CSC），这些细胞负责治疗不成功后肿瘤的重新生长和转移的建立。成功消除癌症的治疗需要考虑到 CSC 亚群的不寻常特性。开发这种治疗策略的一个主要问题是仍然缺乏能够轻松区分 CSC 与其分化后代以及正常组织对应物的方法。从人类肿瘤中纯化癌症干细胞受到患者异质性以及新鲜和大量肿瘤样本的可用性的限制。此外，目前的标记物可富集人类 CSC，但不能完全纯化。根据我们的初步观察，我们提出了一种使用小鼠模型获取和表征口腔上皮正常细胞和癌症干细胞的替代途径。我们的研究中获得的正常舌上皮干细胞与癌症干细胞的基因表达谱可用于鉴定CSC群体中富含的细胞表面或分泌蛋白，这可用于指导人类癌症的鉴定、进一步纯化和血液检测。实验分离的 CSC 还可用于药物筛选，以鉴定特异性靶向癌症干细胞的化合物。此外，癌症研究的一个关键目标是确定癌症干细胞产生和自我更新的机制。具有明确 CSC 的小鼠模型提供了剖析这些过程的时间和功能动态的可能性。 公共卫生相关性：口腔上皮癌是一种常见的恶性肿瘤，死亡率仍然很高。最近的研究表明，肿瘤中含有一小群癌症干细胞（CSC），这些细胞负责治疗失败后肿瘤的重新生长。为了改进当前的治疗，我们需要考虑 CSC 亚群的不寻常特性。我们的总体目标是分离和表征正常和癌症舌上皮干细胞，并表征舌上皮癌干细胞与其分化后代和正常干细胞的不同之处。这可能允许选择性地靶向并消除 CSC，从而改善治疗结果。