Insights into metabolic heterogeneity of colorectal cancer gained from fluorescence lifetime imaging.
Anastasia D KomarovaSnezhana D SinyushkinaIlia D ShchechkinIrina N DruzhkovaSofia A SmirnovaVitaliy M TerekhovArtem M MozherovNadezhda I IgnatovaElena E NikonovaEvgeny A ShirshinLiubov E ShimolinaSergey V GamayunovVladislav I ShcheslavskiyMarina V ShirmanovaPublished in: eLife (2024)
Heterogeneity of tumor metabolism is an important, but still poorly understood aspect of tumor biology. Present work is focused on the visualization and quantification of cellular metabolic heterogeneity of colorectal cancer using fluorescence lifetime imaging (FLIM) of redox cofactor NAD(P)H. FLIM-microscopy of NAD(P)H was performed in vitro in four cancer cell lines (HT29, HCT116, CaCo2 and CT26), in vivo in the four types of colorectal tumors in mice and ex vivo in patients' tumor samples. The dispersion and bimodality of the decay parameters were evaluated to quantify the intercellular metabolic heterogeneity. Our results demonstrate that patients' colorectal tumors have significantly higher heterogeneity of energy metabolism compared with cultured cells and tumor xenografts, which was displayed as a wider and frequently bimodal distribution of a contribution of a free (glycolytic) fraction of NAD(P)H within a sample. Among patients' tumors, the dispersion was larger in the high-grade and early stage ones, without, however, any association with bimodality. These results indicate that cell-level metabolic heterogeneity assessed from NAD(P)H FLIM has a potential to become a clinical prognostic factor.
Keyphrases
- single cell
- prognostic factors
- end stage renal disease
- early stage
- ejection fraction
- newly diagnosed
- high resolution
- high grade
- chronic kidney disease
- single molecule
- radiation therapy
- type diabetes
- high throughput
- stem cells
- cell cycle arrest
- oxidative stress
- patient reported outcomes
- adipose tissue
- endothelial cells
- low grade
- lymph node
- risk assessment
- neoadjuvant chemotherapy
- photodynamic therapy
- wild type