The most important problem of clinical oncology is tumor metastasis. Metabolic switches in tumor cells make a difference for metastases survival and growth in conditions of a new microenvironment. However, they are less explored in comparison with primary tumors metabolism. Fluorescence lifetime imaging microscopy (FLIM), based on recording the decay parameters of cellular autofluorescence emitted by pyridine and flavin cofactors, is considered a promising method for assessing the metabolic status of cells. This study aims to identify differences in the kinetics of NAD(P)H fluorescence decay between metastatic breast cancer cells and the primary tumor, as well as between metastatic cells and lymph node tissue in a 4T1 mouse model. The study revealed a decrease in the relative fraction of free NAD(P)H (a, %), i.e., the fraction not bound to enzymes and associated with glycolysis, in metastases, indicating a shift in the balance toward mitochondrial respiration. Moreover, metastases were metabolically more heterogeneous at the cellular level than primary tumors, as evidenced by a higher dispersion of the mean NAD(P)H fluorescence lifetime τ. Furthermore, metastatic cells were found to have a higher contribution of free NAD(P)H a to fluorescence decay, resulting in a shorter mean lifetime τ compared to lymphoid tissue cells ( 0,001). Thus, this study, using FLIM, demonstrated for the first time differences in the time-resolved characteristics of NAD(P)H autofluorescence between breast cancer metastases and the primary tumor, and between metastases and lymph node tissue. These differences are consistent with existing concepts of the oxidative metabolism of breast cancer metastases. The obtained data are of interest for the search for therapeutic targets in the pathways of energy metabolism of metastases and the development of new approaches to their diagnosis using autofluorescence.
Plekhanov et al. (Wed,) studied this question.