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.
Fatty acid is an important part in the rich repertoire of cancer cell metabolism, which contributes to the development of drug resistance and tumor metastasis. We propose to develop methods for analyzing fatty acid metabolism at single cell level, and plan to incorporate the method into a multiplex microchip platform for quantification of metabolites and proteins from single cells. The implementation of the proposed method will provide new insights into cellular lipid metabolism and cancer biology.
