Decoding Individual Exosomes in Cancer

解码癌症中的个体外泌体

• 批准号: 10440265
• 负责人: GREGORY W FARIS
• 金额: $ 22.63万
• 依托单位: NUMENTUS TECHNOLOGIES INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440265
• 关键词: Address; Biological; Biology; Blood; Blood specimen; Breast Cancer Cell; Breast Cancer cell line; Caliber; Cancer Biology; Cancer Prognosis; Cardiovascular Diseases; Cell Line; Cells; Clinical; Clinical Management; Communication; Detection; Development; Diagnosis; Diagnostic; Disease; Dyes; Gel; Goals; Heat-Shock Proteins 70; Heterogeneity; Homeostasis; Human; Image; Immune response; In Situ; Individual; Label; Lead; Learning; Life; Lipid Bilayers; Lipids; Liposomes; Liquid substance; Malignant Neoplasms; Mammary Neoplasms; Masks; Medicine; Membrane Proteins; Methods; MicroRNAs; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Normal Cell; Nucleic Acids; Oncogenic; Outcome; Pathology; Patients; Physiological Processes; Physiology; Plasma; Polymerase Chain Reaction; Process; Protein Analysis; Proteins; Reading; Recurrence; Research; Reverse Transcription; Sampling; Screening for cancer; Serum; Signal Transduction; Speed; Technology; Testing; Therapeutic; Tissues; Tumor Burden; Tumor-Derived; Work; amplification detection; base; cancer cell; cell type; clinically relevant; design; exosome; extracellular vesicles; fluorescence imaging; imaging platform; imaging system; improved; intercellular communication; liquid biopsy; malignant breast neoplasm; malignant phenotype; nanomedicine; nanoparticle; nanoscale; new technology; novel; novel diagnostics; particle; polyacrylamide gels; prognostic; prognostic tool; prognostic value; stem cell biology; therapeutic nanoparticles; tumor

PROJECT SUMMARY There is increasing recognition that extracellular vesicles (EVs)¾micrometer- or nanometer-sized lipid particles containing protein and nucleic acid cargoes (information)¾are highly promising for new diagnostics/prognostics and even have therapeutic value. There is, however, an unmet need for methods able to solve a fundamental problem confounding the exploitation of EV information in biology and medicine¾EVs are naturally highly heterogeneous particles. In this pilot (R21) project, our experimental goal is to address the need for analyzing EV heterogeneity (subpopulations) by focusing on particles called exosomes. Specifically, our new technology platform is designed to address the problem of resolving bulk exosomal subpopulations by directly correlating surface protein and nucleic acid (microRNA or miRNA) cargoes of single exosomes by performing highly multiplexed fluorescence imaging analysis. Our ultimate goal is to develop a unique imaging platform for the high-throughput, high-content analysis of the protein and nucleic acid cargoes of single exosomes (and other EVs) obtained from any biological sample. This new platform could enable novel diagnostic/prognostic “liquid biopsy” tests for managing cancers as well as other pathologies, such as neurodegenerative and cardiovascular diseases. To achieve our experimental goal, in the work for Aims 1 and 2 we will develop and optimize our imaging platform for experimental multiplexed analysis of human breast cancer cell exosomes and their miRNA cargoes. These Aims will validate our platform for in situ miRNA analysis of single exosomes from cancer cells with documented exosomal miRNA signatures. During Aim 3, we will use the validated platform to correlate the surface protein display and miRNA cargo of individual exosomes released by human breast cancer cell lines representing early- and late-stage cancers and compare these with a normal cell line control. Aim 3 will test the capability of our platform to resolve exosomal subpopulations in an original bulk sample, based on correlated signals for surface proteins and miRNA cargoes of single exosomes. We propose that our novel imaging platform has the potential to become a new diagnostic/prognostic tool for the clinical management of breast cancer, other tumor types, and other pathologies in which EV/exosomal analysis could provide clinically useful information. Recent research demonstrates that breast-cancer-cell- derived exosomes can transport cargoes that promote oncogenic or malignant phenotypes. Thus, exosomes released from breast tumors could carry information with critical diagnostic/prognostic value, which could be sampled from blood or other patient fluids (a “liquid biopsy”). This capability may also assist in developing exosome-based therapies for human tumor types.

项目总结