Metabolic Rewiring Promotes AA PCa by Regulating Stromal-Epithelial Interaction

代谢重新布线通过调节间质-上皮相互作用促进 AA PCa

• 批准号: 10201526
• 负责人: Ganesh S Palapattu
• 金额: $ 37.94万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201526
• 关键词: 6-Phosphofructo-2-kinase; Address; Adenosine; African; African American; American; Amphotericin B; Benign; Biochemical; Biochemical Markers; Bioinformatics; Biological; Biological Assay; Biological Markers; Biological Process; Biometry; CD44 gene; Cancer Biology; Cancer Patient; Carbon; Cells; Cellular Metabolic Process; Clinical; Clinical Management; Collagen; Collection; Data; Development; Diagnostic; Drug Targeting; Enzymes; Epidemiology; Epithelial-Stromal Communication; European; Foundations; Fructose; Future; Genes; Glean; Glucose; Glycolysis; In Vitro; Incidence; Inosine; Knowledge; Link; Malignant neoplasm of prostate; Mass Spectrum Analysis; Measures; Mediator of activation protein; Metabolic; Metabolic Marker; Metabolism; Microarray Analysis; NADP; Operative Surgical Procedures; Organ; Pathologic; Pathology; Pathway interactions; Patients; Pentosephosphate Pathway; Phenotype; Plasma; Production; Property; Prostate; Prostatectomy; Purine Nucleotides; Recurrence; Regulation; Research; Risk; Role; Route; Sampling; Science; Smooth Muscle Actin Staining Method; Stromal Cells; Techniques; Tenascin; Testing; Therapeutic; Time; Tissue Microarray; Tissues; Training; Translating; Tumor Cell Migration; Urine; adenosine deaminase; arm; base; biomarker panel; cancer health disparity; cancer recurrence; case control; clinical predictors; epidemiologic data; follow-up; health disparity; in vivo; insight; men; metabolome; metabolomics; novel; nucleotide metabolism; overexpression; predictive marker; prognostic; prostate cancer cell; prostate cancer cell line; prostate cancer model; small molecule; therapeutic target; tumor; tumor metabolism; tumor microenvironment; tumor progression

The long-term objective of our research plan is to reduce the disproportionate effects of prostate cancer on African American men. In this application, we have used the technique of metabolomic profiling to uncover underlying biochemical differences between prostate cancers of African American and European American origin. Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules) that are the byproducts of cellular metabolism. That is to say, in this kind of analysis we are measuring the biochemical entities (or metabolites) that are produced by the functional machinery of the cell. With knowledge of the identity of specific metabolites we can infer the biological processes that produced them, thus gaining insight into a cell’s metabolism. Given this, a guiding principle of application is that unique biochemical differences exist between prostate cancers of African American and European American origin and that these differences can influence the tumors and their surrounding cells termed stroma such that together they can promote the progression of the tumors. Since African American prostate cancer grow and progress more rapidly than European American tumors, our studies will potentially address some of the causes underlying prostate cancer health disparity. In addition, it will also build a first-of-its-kind biomarker panel that can predict cancer recurrence in ancestry verified African American men with prostate cancer. In this proposal, we will i) identify the biochemical mechanism that drives elevated levels of inosine in African American Prostate Cancer, ii) evaluate the function of elevated inosine in making African American tumors aggressive and invoke tumor promoting properties in the surrounding stromal cells and iii) develop plasma based metabolic markers for biochemical recurrence in African American men. At the conclusion of this study, we will have developed a racially derived metabolomic model for prostate cancer as well as identified candidate pathways for future drug targeting. We would have also built a proof-of-principle metabolite-based test with the ability to predict cancer recurrence based on the ancestry of the patient. In the longer term, this test will be validated and translated into a clinical assay that should have the ability to predict the recurrence of prostate cancer in an ancestry informed fashion in prostate cancer patients.

我们研究计划的长期目标是减少前列腺癌对患者的不成比例的影响。 非裔美国人在本申请中，我们使用代谢组学分析技术来揭示 非洲裔美国人和欧洲裔美国人前列腺癌之间的潜在生化差异 起源代谢组学描述了定量代谢物水平的科学（例如，小分子）， 是细胞新陈代谢的副产品也就是说，在这种分析中， 由细胞的功能机制产生的生化实体（或代谢物）。用知识 特定代谢物的身份，我们可以推断产生它们的生物过程，从而获得 深入了解细胞的新陈代谢鉴于此，应用的指导原则是，独特的生物化学 非洲裔美国人和欧洲裔美国人起源的前列腺癌之间存在差异， 差异可以影响肿瘤及其周围称为基质的细胞， 促进肿瘤的发展。由于非裔美国人前列腺癌的生长和进展更多 我们的研究可能会解决一些潜在的原因， 前列腺癌的健康差距。此外，它还将建立一个首创的生物标志物面板，可以预测 癌症复发的祖先证实非洲裔美国男性前列腺癌。在本建议书中，我们将（i） 确定驱动非裔美国人前列腺癌中肌苷水平升高的生化机制， ii）评估升高的肌苷在使非裔美国人肿瘤侵袭性和诱发肿瘤中的作用， 促进周围基质细胞中的特性，和iii）开发基于血浆的代谢标记物， 非裔美国人的生化复发。在这项研究结束时，我们将制定一个 前列腺癌的种族衍生代谢组学模型以及未来药物的候选途径 面向.我们还将建立一个基于代谢物的原理验证测试，能够预测癌症 根据患者的祖先复发。从长远来看，这项测试将得到验证和翻译 进入临床分析，应该有能力预测前列腺癌的复发在一个祖先， 前列腺癌的治疗方法