Insights into metabolic heterogeneity of colorectal cancer gained from fluorescence lifetime imaging
Anastasia D Komarova,
Snezhana D Sinyushkina,
Ilia D Shchechkin,
Irina N Druzhkova,
Sofia A Smirnova,
Vitaliy M Terekhov,
Artem M Mozherov,
Nadezhda I Ignatova,
Elena E Nikonova,
Evgeny A Shirshin,
Liubov E Shimolina,
Sergey V Gamayunov,
Vladislav I Shcheslavskiy,
Marina V Shirmanova
Affiliations
Anastasia D Komarova
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russian Federation
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Ilia D Shchechkin
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russian Federation
Irina N Druzhkova
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Sofia A Smirnova
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Nadezhda I Ignatova
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Elena E Nikonova
Laboratory of Clinical Biophotonics, Sechenov First Moscow State Medical University, Moscow, Russian Federation
Evgeny A Shirshin
Laboratory of Clinical Biophotonics, Sechenov First Moscow State Medical University, Moscow, Russian Federation; Faculty of Physics, Lomonosov Moscow State University, Moscow, Russian Federation
Liubov E Shimolina
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation; Becker&Hickl GmbH, Berlin, Germany
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.
