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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。

基本信息

批准号：
8242000
负责人：
Agnieszka Kobielak
金额：
$ 20.25万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8242000
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 public health relevance self-renewal slow potential stem cell population therapy development therapy resistant tongue sampling treatment strategy tumor young adult

项目摘要

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，每年在美国影响40，000名新患者。这种疾病的死亡率仍然很高，因为远处转移的发展和治疗耐药的局部和区域复发的出现。头颈部鳞状细胞癌（HNSCC）诊断时的中位年龄传统上和历史上被设定为60岁。然而，在40岁以下的年轻人中，起源于口腔和口咽部的一部分肿瘤的发病率一直在稳步快速增长。此外，舌癌似乎占发病率增加的大部分，现已成为口腔中第二常见的恶性肿瘤。最近的研究表明，肿瘤的形成可能是由于癌症干细胞的发展。根据这一假设，肿瘤含有一小群癌症干细胞（CSC），其负责在不成功的治疗后肿瘤的再生长和转移的建立。成功的治疗，以消除癌症需要考虑到不寻常的性质的CSC亚群。开发这种治疗策略的主要问题是仍然缺乏可以容易地将CSC与其分化的后代以及与其正常组织对应物区分开的方法。从人肿瘤中纯化癌症干细胞受到患者异质性和新鲜且相当大的肿瘤样品的可用性的限制。此外，目前的标记物富集但不允许完全纯化人CSC。基于我们的初步观察，我们提出了一种替代途径，获得和表征口腔上皮正常和癌症干细胞使用小鼠模型。本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群体中富集的细胞表面或分泌蛋白，其可用于指导人类癌症的鉴定、进一步纯化和基于血液的检测。实验分离的CSC也可用于药物筛选，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。具有确定CSC的小鼠模型提供了解剖这些过程的时间和功能动力学的可能性。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再生长。为了改善目前的治疗方法，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差异。这可能允许选择性地靶向并消除CSC，从而改善治疗结果。