Profiling fatty acid uptake and activity in single tumor cells

分析单个肿瘤细胞的脂肪酸摄取和活性

• 批准号: 9904572
• 负责人: Wei Wei
• 金额: $ 8.13万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904572
• 关键词: Acids; Amino Acids; Azides; Bar Codes; Binding; Biological; Biological Assay; Biological Process; Biomass; Blood Circulation; Buffers; Cancer Biology; Cancer Cell Growth; Cancer Patient; Carbon; Cell Maturation; Cell Proliferation; Cell Survival; Cells; Cellular Assay; Chemicals; Chemistry; Combined Modality Therapy; Cysteine; Cytolysis; Detection; Disease; Drug resistance; Ensure; Enzymes; Exhibits; Fatty Acids; Fluorescence Resonance Energy Transfer; Genetic Variation; Glioblastoma; Glucose; Glutamine; Gold; Growth; Heterogeneity; Human; Immobilization; Immune; Intervention; Lead; Length; Ligation; Malignant Neoplasms; Metabolic; Metabolic Pathway; Metabolism; Methods; Microfluidics; Modeling; Molecular; Neoplasm Metastasis; Nutrient; Nutritional; Oncogenic; Pathway interactions; Pattern; Performance; Pharmaceutical Preparations; Phenotype; Phosphoproteins; Procedures; Refractory; Reproducibility; Research; Resistance; Resolution; Role; Sampling; Scheme; Signal Pathway; Signal Transduction; Signaling Protein; Source; Stress; Surface; Technology; Testing; Therapeutic; Toxic effect; Transportation; Variant; Work; acyl-CoA dehydrogenase; analog; anticancer research; base; cancer cell; cancer stem cell; cinnamic acid; design; drug development; experimental study; fatty acid analog; fatty acid metabolism; flexibility; glucose metabolism; inhibitor/antagonist; insight; lipid metabolism; long chain fatty acid; lucifer yellow; microchip; neoplastic cell; oxidation; performance tests; programs; protein metabolite; single cell proteins; stem cell differentiation; stem cell population; targeted treatment; therapy development; tool; tumor; tumor growth; tumor heterogeneity; tumor metabolism; uptake

Project summary/Abstract Profiling fatty acid uptake and activity in single tumor cells (PIs: Min Xue, UC Riverside; Wei Wei, UCLA) Altered fatty acid metabolism is involved in many types of diseases, as exemplified in cancer. Many cancer cells exhibit elevated fatty acid uptake and metabolic activity. In these cells, fatty acids can be used as alternative energy fuels or biomass building blocks to support the uncontrolled growth, defend stress and promote metastasis. Because cancer cells are extremely heterogeneous, their activities on fatty acid uptake and metabolism are expected to vary significantly even within the same tumor sample. Similar to the heterogeneity involving other metabolic and signaling pathways, the variation in fatty acid metabolism also contribute to the cell plasticity. This variation helps cancer cells adapt to nutritional, environmental and therapeutic stress, and facilitates the development of drug resistance and metastatic lesions. Therefore, the ability to analyze cellular fatty acid metabolism, especially at single cell level, promises more insights to cancer biology. In this proposal, we aim to develop a surface-based chemical method for quantifying fatty acid uptake as well as its metabolic activities in single cells. We will first synthesize a panel of fatty acid analogs, and use cell uptake experiments to validate their utility as probes for assessing cellular fatty acid uptake and its related metabolic activities. We will employ surface-based detection schemes to quantify the selected probes. Subsequently, we seek to incorporate this detection method into a well-established microfluidics-based single cell analytical platform. Successful implementation of the proposed work will provide a tool for analyzing fatty acid uptake and metabolic activity at single cell resolution. In addition, we will be able to perform multiplexed analysis to study the interplay between fatty acid metabolism and other metabolic and oncogenic signaling pathways, which may provide therapeutic implications that cannot be easily revealed by bulk-level analysis.

项目摘要/摘要 分析单个肿瘤细胞的脂肪酸摄取和活性(PI：闵雪，加州大学河滨分校；魏微，加州大学洛杉矶分校) 脂肪酸代谢改变与许多类型的疾病有关，例如癌症。许多癌症 细胞表现出更高的脂肪酸摄取和代谢活性。在这些细胞中，脂肪酸可用作 替代能源燃料或生物质积木，以支持不受控制的增长，抵御压力和 促进转移。由于癌细胞的异质性极强，它们在摄取脂肪酸方面的活性 即使在同一个肿瘤样本中，新陈代谢也会有很大的不同。类似于 涉及其他代谢和信号通路的异质性，脂肪酸代谢的变化也 有助于细胞的可塑性。这种变异有助于癌细胞适应营养、环境和 治疗压力，并促进耐药和转移病变的发展。因此， 分析细胞脂肪酸代谢的能力，特别是在单细胞水平上，有望对癌症有更多的洞察力 生物学。在这项建议中，我们的目标是开发一种基于表面的化学方法来量化脂肪酸的摄取。 以及它在单细胞中的代谢活动。我们将首先合成一组脂肪酸类似物，并使用 细胞摄取实验验证其作为评估细胞脂肪酸摄取及其相关探针的有效性 代谢活动。我们将使用基于表面的检测方案来量化选定的探针。 随后，我们试图将这种检测方法整合到一种成熟的基于微流控技术的单一 细胞分析平台。拟议工作的成功实施将为分析脂肪组织提供一个工具 单细胞分辨率下的酸摄取和代谢活性。此外，我们将能够执行多路传输 分析研究脂肪酸代谢与其他代谢和致癌信号的相互作用 途径，这可能提供不容易通过整体水平分析揭示的治疗影响。