The Detection, Isolation and Characterization of Disseminated Tumor Cells

前列腺癌(CAP)转移，尤其是骨转移，是导致严重发病率和死亡率的原因。 由于所有的转移都来自于播散性肿瘤细胞(DTC)，因此对DTC的研究对我们的 了解转移过程和设计新的治疗策略。在过去，田野 通常专注于检测循环或骨髓中这些脱落细胞。我们有 最近，我们把注意力转向了DTC的特征，这是进一步深入了解DTC的必要条件。 我们假设DTC的特定基因组和/或基因表达谱将对 前列腺癌根治术后的生化衰竭和雄激素消融的反应持续时间。另外，我们 预测这些DTC曲线将与原发肿瘤的DTC曲线显著不同。 我们还假设，一些DTC具有癌症干细胞特性，而其他DTC则分离自 手术后没有疾病证据(NED)的患者具有休眠肿瘤细胞的特征。 我们的具体目标如下： 目的#1：检测、分离和鉴定前列腺癌根治术前高血糖患者的DTC 复发风险(Gleason sum&gt；6)与原发肿瘤的预后和概况相关。 目的#2：检测、分离和鉴定接受雄激素治疗的患者的DTC 骨转移瘤与非骨转移瘤的轮廓比较。 目标3：确定DTC在干细胞属性、肿瘤细胞休眠等方面的生物学功能 与骨转移相关的标志物，如IGF-IR、RUNX2和TMPRSS2-ERG基因融合。 这三个目标的成功实现将提供对生物特征的相当大的洞察力 戴帽子的DTC。它还可以提供一种机制，由此检测到DTC的基因组图谱(A) 疾病的早期可能预示复发，以及(B)疾病的晚期可能预测 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在某些情况下 例如，这些DTC模仿癌症干细胞，而在其他例子中，它们描绘了肿瘤细胞的休眠状态。 相关性(请参阅说明)： 由于所有的转移都来自于播散性肿瘤细胞(DTC)，因此对DTC的研究对我们的 对转移过程的理解。这些细胞的生物学和分子特征在很大程度上 由于分离困难和获得的用于研究的细胞很少，因此未知。我们已经取得了重大进展 在这一领域取得了进展，并准备探索干细胞和休眠等潜在属性。

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.