CANCER STEM CELL LONGEVITY AND METASTATIC POTENTIAL IN BLADDER CANCER

膀胱癌的癌症干细胞寿命和转移潜力

• 批准号: 8171697
• 负责人: Bruce A Buchholz
• 金额: $ 4.25万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171697
• 关键词: Accounting; Age; Biological Assay; Bladder Neoplasm; Cancer cell line; Cell Cycle; Cell Separation; Cells; Cisplatin; Computer Retrieval of Information on Scientific Projects Database; DNA; Development; Funding; Goals; Grant; Human; Individual; Institution; Label; Literature; Longevity; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Medical History; Methods; Modeling; Neoplasm Metastasis; Patients; Population; Population Heterogeneity; Property; Radiation; Radio; Relapse; Reporting; Research; Research Personnel; Resistance; Resources; Role; Sampling; Side; Source; Stem cells; TimeLine; Tracer; United States National Institutes of Health; Work; anticancer research; base; cancer cell; cancer stem cell; cancer therapy; chemotherapeutic agent; chemotherapy; falls; improved; response; stem; stem cell population; therapy development; tool; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent studies on stem-like cancer cells (SLCC) suggest a potential reason for the low efficacy of current cancer therapies and a way to improve them. Current cancer chemo- and radio-therapies target the rapidly-dividing cells in a tumor, however a tumor is a heterogeneous population of cells. Comprising a small amount of the population, SLCC remain relatively static and initiate the proliferative cells that account for the majority of the tumor mass. These SLCC are essentially dormant and resistant to chemo- and radio-therapy. SLCC remain after therapy and retain their ability to initiate proliferative cancer cells; therefore it is believed SLCC are the source of metastasis and relapse. However, there is controversy over the definition of SLCC and their role in cancer development and progression. Using bladder cancer as a model, we aim to show SLCC in bladder cancer tumors are much older than the bulk of the tumor, resistant to conventional chemo- and radio-therapy and responsible for metastasis and relapse. The first part of the project involves isolating stem cell populations from three bladder cancer cell lines with a range of responses to the chemotherapeutic agent, cisplatin. The cycling of these cells will be examined in addition to their ability to demonstrate properties associated with stem cells as demonstrated through colony-forming assays, long term proliferation, differentiation and response to chemotherapy and radiation. Initially we plan to isolate CD44+,CD66C- as our stem cell population, as this has the strongest support in the literature. A side-scatter population has also been reported to possess stem cell capabilities in several bladder cancer lines and may also be investigated. The second goal of the project is to investigated SLCC in fresh human bladder tumor samples. The age of SLCC isolated from fresh tumor samples along with non-stem cells will be determined using the 14C bomb curve with AMS. The elevation of 14C/C in the DNA of these sorted cells will be used to assign a date of synthesis. This date of synthesis can be compared to the medical history of the patient in order to determine where on the timeline of tumor development SLCC fall. Finally, we will develop a new tool for use in cancer research by producing SLCC with highly labeled DNA. Labeled cancer stem cells will be produced from one of the lines used in the initial part of the project based upon the percentage of stem cells and cell cycle properties. These labeled SLCC can then be used in research on their metastatic potential and as a tracer in cancer research. AMS will allow us to follow individual cells. This work has the power to transform the current methods used to treat cancer. Existing therapies are developed primarily against the highly proliferative cells that make up the bulk of the tumor. By definitively measuring the longevity of SLCC, they can be confirmed as the reason for relapse and metastasis. The creation of labeled SLCC will provide a new tool to be used in cancer research and change the direction of the field.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 关于干癌细胞（SLCC）的最新研究表明，当前癌症疗法效力低的潜在原因和改善它们的方法。 当前的癌症化学和放射性治疗靶向肿瘤中快速分散的细胞，但是肿瘤是一种异质的细胞群。 SLCC包括少量人群，保持相对静态，并启动占大多数肿瘤质量的增殖细胞。 这些SLCC本质上是休眠的，对化学和放射治疗具有抵抗力。 SLCC在治疗后仍保留，并保留其启动增生性癌细胞的能力。因此，据信SLCC是转移和复发的来源。 但是，关于SLCC的定义及其在癌症发展和进展中的作用存在争议。 我们使用膀胱癌作为模型，旨在显示膀胱癌肿瘤中的SLCC比大部分肿瘤大得多，对常规化疗和放射治疗具有抵抗力，并负责转移和复发。 该项目的第一部分涉及从三个膀胱癌细胞系中分离出对化学治疗剂Cisplatin的一系列反应的干细胞群。 除了证明与干细胞相关的特性外，还将检查这些细胞的循环，这是通过菌落形成测定，长期增殖，分化和对化学疗法和放射线的反应所证明的。 最初，我们计划将CD44+，CD66C-作为干细胞群体分离，因为这在文献中具有最强的支持。 据报道，还据报道，在几个膀胱癌系中具有干细胞能力，也可以研究。 该项目的第二个目标是研究新鲜人膀胱肿瘤样品中的SLCC。 将使用AMS的14C炸弹曲线确定从新鲜肿瘤样品中分离出的SLCC年龄。这些排序细胞的DNA中14C/C的升高将用于分配合成日期。 可以将合成日期与患者的病史进行比较，以确定SLCC肿瘤发育时间的位置。 最后，我们将通过生产具有高标记DNA的SLCC来开发一种用于癌症研究的新工具。 根据干细胞的百分比和细胞周期特性，将从项目初始部分中使用的一条线之一产生标记的癌症干细胞。 然后，这些标记的SLCC可以用于研究其转移潜力和癌症研究的示踪剂。 AM将允许我们跟随单个细胞。 这项工作有能力改变用于治疗癌症的当前方法。 现有的疗法主要是针对构成大部分肿瘤的高度增殖细胞的开发。 通过确定测量SLCC的寿命，可以将其确认为复发和转移的原因。 标记为SLCC的创建将为癌症研究提供一种新工具，并改变该领域的方向。