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Metabolic coupling between a single tumor cell and fibroblasts on microdroplet array chips
Jian Zhao1, Xinxing Miao1, Xiang Xiao1
1Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu Province 215123, P. R. China. jliu@suda.edu.cn.
Tumor cells and fibroblasts interact via nitric oxide (NO) signaling, enhancing tumor aggressiveness. A new microdroplet platform reveals how fibroblast NO production boosts tumor cell matrix metalloproteinase-9 (MMP-9) activity.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Cell Biology
Background:
- Tumor-stroma interactions, specifically metabolic coupling between cancer cells and fibroblasts, are crucial for tumor aggressiveness.
- Matrix metalloproteinase-9 (MMP-9) activity, regulated by nitric oxide (NO), is a key factor in tumor progression.
- Studying these interactions at the single-cell level is essential but challenging.
Purpose of the Study:
- To develop a microdroplet array platform for investigating single-cell interactions between tumor cells and fibroblasts.
- To elucidate the role of inducible nitric oxide synthase (iNOS)-dependent NO signaling in metabolic coupling between tumor cells and fibroblasts.
- To understand how this coupling influences tumor cell aggressiveness, specifically MMP-9 activity.
Main Methods:
- Co-encapsulation of single tumor cells (HeLa, MCF-7) and fibroblasts (3T3-L1) in a microdroplet array.
- Investigation of nitric oxide (NO) signaling pathways, including the role of inducible nitric oxide synthase (iNOS).
- Assessment of matrix metalloproteinase-9 (MMP-9) activities and the effect of L-NAME (an inhibitor).
- Analysis of correlations between fibroblast lipid droplet accumulation and tumor cell aggressiveness using microchips.
Main Results:
- Fibroblasts significantly enhance tumor cell MMP-9 activities through an iNOS-dependent NO signaling pathway.
- Inhibition of this pathway with L-NAME effectively disrupts the metabolic coupling and reduces MMP-9 activity.
- Phenotype-dependent correlations were observed between fibroblast lipid droplet accumulation and tumor cell aggressiveness.
Conclusions:
- Metabolic coupling mediated by fibroblast-derived NO is a critical driver of tumor cell aggressiveness.
- The microdroplet array platform is effective for studying single-cell level tumor-stroma interactions.
- Metabolic competition and enzymatic regulation play joint roles in shaping tumor-stroma crosstalk.
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