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

基本信息

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
项目类别：
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

项目摘要

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人类的不成比例的影响在此应用中，我们使用代谢组学分析技术来揭示非洲裔美国男性。非裔美国人和欧洲裔美国人前列腺癌之间潜在的生化差异代谢组学描述了量化代谢物（例如小分子）水平的科学。是细胞代谢的副产品也就是说，在这种分析中我们测量的是由细胞的功能机制通过知识产生的生化实体（或代谢物）。根据特定代谢物的身份，我们可以推断产生它们的生物过程，从而获得鉴于此，应用的指导原则是独特的生化作用。非裔美国人和欧洲裔美国人起源的前列腺癌之间存在差异，并且这些差异差异可以影响肿瘤及其周围的细胞（称为基质），这样它们就可以一起发挥作用促进肿瘤的进展，因为非裔美国人前列腺癌的生长和进展更多。比欧洲和美国的肿瘤发生得更快，我们的研究将有可能解决一些根本原因此外，它还将建立一个可以预测前列腺癌健康差异的首个生物标志物组合。经证实患有前列腺癌的非裔美国男性的癌症复发在本提案中，我们将 i) 确定导致非洲裔美国人前列腺癌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具有侵袭性并诱发肿瘤方面的功能促进周围基质细胞的特性，以及 iii) 开发基于血浆的代谢标记物非洲裔美国男性的生化复发在这项研究结束时，我们将开发出一种方法。前列腺癌的种族衍生代谢组学模型以及确定的未来药物候选途径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。从长远来看，该测试将得到验证和翻译。进行临床检测，应该能够预测祖先中前列腺癌的复发前列腺癌患者的知情时尚。