Development of a Single-Cell Spatial Metabolomics Method for the Characterization of Cell-Cell Metabolic Interactions

Area of Science:

• Metabolomics
• Cancer Biology
• Cellular Interactions

Background:

• The tumor microenvironment (TME) is complex, with metabolic interactions influencing tumor progression and treatment resistance.
• Understanding cell-cell metabolic crosstalk is crucial for identifying tumor vulnerabilities.

Purpose of the Study:

• To develop and apply a single-cell spatial metabolomics method for profiling metabolic signatures and interactions within the TME.
• To investigate metabolic alterations in cancer cells and fibroblasts upon co-culture.

Main Methods:

• Optimized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for single-cell spatial metabolomics.
• Detected and imaged low-molecular-weight metabolites and lipids in various cancer cell lines and cancer-fibroblast co-cultures.

Main Results:

• Successfully profiled cell-specific metabolic signatures and cell-cell metabolic interactions.
• Observed significant increases in glutamate and aspartate in fibroblasts co-cultured with cancer cells.
• Identified altered fatty acid and phospholipid expressions in both tumor cells and fibroblasts due to co-culture, indicating metabolic competition.

Conclusions:

• The developed single-cell spatial metabolomics method enables detailed analysis of metabolic interactions in complex cellular systems.
• Metabolic reprogramming in cancer cells and fibroblasts during co-culture highlights potential therapeutic targets within the TME.