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

基本信息

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
项目类别：
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

项目摘要

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/摘要在单个肿瘤细胞中分析脂肪酸的摄取和活性（PIS：Min Xue，UC Riverside； Wei Wei，UCLA）脂肪酸代谢改变参与了许多类型的疾病，例如癌症。许多癌症细胞表现出脂肪酸的摄取和代谢活性的升高。在这些细胞中，脂肪酸可以用作替代能源燃料或生物质构建区块，以支持不受控制的增长，捍卫压力和促进转移。因为癌细胞极为异质，所以它们对脂肪酸摄取的活性即使在同一肿瘤样本中，新陈代谢也有明显变化。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可塑性。这种变异有助于癌细胞适应营养，环境和治疗应激，并促进耐药性和转移性病变的发展。因此，分析细胞脂肪酸代谢的能力，尤其是在单细胞水平上，有望对癌症有更多见解生物学。在此提案中，我们旨在开发一种基于表面的化学方法来量化脂肪酸的摄取以及其在单细胞中的代谢活性。我们将首先合成一组脂肪酸类似物，然后使用细胞摄取实验以验证其效用作为评估细胞脂肪酸摄取及其相关的探针代谢活动。我们将采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纳入基于微流体的单一单一细胞分析平台。拟议工作的成功实施将为分析脂肪提供工具单细胞分辨率下的酸摄取和代谢活性。另外，我们将能够执行多路复用分析研究脂肪酸代谢与其他代谢和致癌信号之间的相互作用途径可能会提供治疗意义，而批量分析无法轻易揭示。