The Detection, Isolation and Characterization of Disseminated Tumor Cells

前列腺癌（CaP）转移，特别是骨转移，是导致显著发病率和死亡率的原因。 由于所有的转移瘤都起源于播散性肿瘤细胞（DTC），因此对DTC的研究对我们的研究至关重要。 了解转移过程和设计新的治疗策略。在过去，该领域 一般集中在检测循环或骨髓中的这些脱落细胞。我们有 最近，我们的注意力转向DTC的表征，这是进一步深入了解的必要条件。 我们假设DTC的特异性基因组和/或基因表达谱将是DTC的预后因素。 根治性前列腺切除术后生化衰竭和雄激素消融反应持续时间。另外我们 预测在这些DTC谱与原发肿瘤的那些谱之间将观察到显著差异。 我们还假设，一些DTC具有癌症干细胞属性，而另一些DTC从肿瘤干细胞中分离出来。 手术后没有疾病证据（NED）的患者具有休眠肿瘤细胞的属性。 我们的具体目标如下： 目标#1：检测、分离和表征来自根治性直肠癌切除术前高血糖患者的DTC 复发风险（Gleason总和>6），并与原发性肿瘤的结局和特征相关。 目的#2：检测、分离和表征来自接受雄激素消融的患者的DTC， 与骨和非骨转移瘤的特征比较。 目的#3：定义DTC在干细胞属性、肿瘤细胞休眠方面的生物学功能 以及与骨转移相关的标记物，例如IGF-IR、RUNX 2和TMPRSS 2-ERG基因融合。 这三个目标的成功实现将提供对生物学特性的相当深入的了解。 在CaP中的DTC。它还可以提供一种机制，由此检测到的DTC的基因组谱（a） 疾病早期可预测复发，（B）疾病晚期可预测复发的持续时间。 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一些 在某些情况下，这些DTC模拟癌症干细胞，而在其他情况下，它们描绘肿瘤细胞休眠。 相关性（参见说明）： 由于所有的转移瘤都起源于播散性肿瘤细胞（DTC），因此对DTC的研究对我们的研究至关重要。 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 由于在分离中的挑战和获得用于研究的非常少的细胞而未知。我们已经取得了重大进展 我们正在研究这一领域的进展，并准备探索潜在的属性，如干细胞和休眠。

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.