The Detection, Isolation and Characterization of Disseminated Tumor Cells

播散性肿瘤细胞的检测、分离和表征

• 批准号: 8303429
• 负责人: ROBERT Louis VESSELLA
• 金额: $ 59.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8303429
• 关键词: Ablation; Androgens; Area; Aspirate substance; Attention; Autopsy; Biochemical; Biological; Blood Circulation; Bone Marrow; Cells; Clinical; Collaborations; Data; Detection; Diagnosis; Disease; ERG gene; Evolution; Failure; Fred Hutchinson Cancer Research Center; Gene Expression; Gene Fusion; Genes; Genomics; Gleason Grade for Prostate Cancer; In Vitro; Institutes; Instruction; Investigation; Laboratories; Malignant neoplasm of prostate; Metastatic Neoplasm to the Bone; Molecular; Molecular Profiling; Morbidity - disease rate; Neoplasm Metastasis; No Evidence of Disease; Operative Surgical Procedures; Outcome; Patients; Pattern; Population; Primary Neoplasm; Process; Radical Prostatectomy; Recurrence; Research Personnel; Sampling; Science; Series; Stem cells; Stromal Cells; TMPRSS2 gene; Technology; Time; Washington; Xenograft Model; advanced disease; bone; cancer stem cell; comparative genomic hybridization; design; follow-up; fusion gene; high risk; in vivo; insight; metastatic process; mortality; neoplastic cell; novel therapeutics; peripheral blood; prognostic; programs; response; stem

Prostate cancer (CaP) metastases, especially to bone, are the cause of significant morbidity and mortality. Since all metastases emanate from disseminated tumor cells (DTC), the study of DTC is critical to our understanding of the metastatic process and the design of novel therapeutic strategies. In the past, the field has generally focused on the detection of these shed cells in the circulation or in bone marrow. We have recently turned our attention to the characterization of DTC which is imperative for further insight. We hypothesize that specific genomic and/or gene expression profiles of the DTC will be prognostic for both biochemical failure post radical prostatectomy and duration of response to androgen ablation. Also, we predict significant differences will be observed between these DTC profiles and those of the primary tumor. We also hypothesize that some of the DTC have cancer stem cell attributes while others isolated from patients who have no evidence of disease (NED) after surgery have attributes of dormant tumor cells. Our Specific Aims are as follows: Aim #1: Detect, isolate and characterize the DTC from patients pre-radical prostatectomy who are at high risk (Gleason sum >6) of recurrence and correlate to outcome and profiles of the primary tumor. Aim #2: Detect, isolate and characterize the DTC from patients undergoing androgen ablation with comparison of profiles to that of bone and non-bone metastases. Aim #3: Define the biological functionality of DTC with regard to stem cell attributes, tumor cell dormancy and markers associated with bone metastases such as IGF-IR, RUNX2, and TMPRSS2-ERG gene fusions. The successful execution of these three aims will provide considerable insight on the biological character of the DTC in CaP. It may also provide a mechanism whereby the genomic profile of the DTC detected (a) eariy in disease may be predictive of recurrence and (b) late in disease may be predictive of the duration of response to androgen ablation. Finally, one of the most exciting aspects is our quest to determine if in some instances these DTC mimic cancer stem cells while in others they portray tumor cell dormancy. RELEVANCE (See instructions): Since all metastases emanate from disseminated tumor cells (DTC), the study of DTC is critical to our understanding of the metastatic process. The biological and molecular character of these cells is largely unknown due to challenges in isolation and the very few cells obtained for study. We've made significant advances in this area and are prepared to explore potential attributes such as stem-cellness and dormancy.

前列腺癌（CAP）转移，尤其是对骨骼的转移，是发病率明显的原因。 由于所有转移来自散布的肿瘤细胞（DTC），因此DTC的研究对我们来说至关重要 了解转移过程和新型治疗策略的设计。过去，领域 通常集中于检测循环中或骨髓中这些细胞的检测。我们有 最近，我们将注意力转移到了DTC的表征上，这对于进一步的见识必须。 我们假设DTC的特定基因组和/或基因表达谱将是预后的 从根治性前列腺切除术和对雄激素消融的反应持续时间后，生化衰竭均两种衰竭。另外，我们 预测这些DTC谱和原发性肿瘤的谱图将观察到显着差异。 我们还假设某些DTC具有癌细胞属性，而另一些则与 手术后没有疾病（NED）的患者具有休眠的肿瘤细胞。 我们的具体目的如下： AIM＃1：检测，分离和表征DTC的DTC，患者的前列腺切除术较高 复发的风险（Gleason和6），并与原发性肿瘤的结果和特征相关。 AIM＃2：检测，分离和表征来自接受雄激素消融患者的DTC 比较曲线与骨骼和非骨转移的比较。 目标＃3：定义DTC在干细胞属性，肿瘤细胞休眠方面的生物学功能 以及与IGF-IR，RUNX2和TMPRSS2-GER基因融合的骨转移相关的标记。 这三个目标的成功执行将提供对生物特征的大量见解 DTC的帽子。它还可以提供一种机制，从而使检测到DTC的基因组谱（a） 疾病的耳朵可能可以预测复发，并且（b）疾病后期可能可以预测 对雄激素消融的反应。最后，最令人兴奋的方面之一是我们寻求确定是否在某些 实例这些DTC模拟癌症干细胞，而在其他情况下它们描绘了肿瘤细胞休眠。 相关性（请参阅说明）： 由于所有转移来自散布的肿瘤细胞（DTC），因此DTC的研究对我们来说至关重要 了解转移过程。这些细胞的生物学和分子特征在很大程度上是 由于孤立的挑战而未知，并且获得了很少的细胞进行研究。我们变得很重要 该领域的进步，并准备探索诸如干细胞和休眠等潜在属性。