Optical Metabolic Imaging of Tumors to Quantify Reactive Oxygen Species
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2022-04-13
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Abstract
The growth and development of cancer cells differs from that of normal cells. Cancer cells exhibit increased metabolic activity and have increased production of highly reactive molecules called Reactive Oxygen Species (ROS), which serve as regulators of important signaling pathways and promote many aspects of tumor growth and progression. Factors such as environmental changes, genetic mutations, and changes in the cellular and extracellular mechanical properties stimulate metabolic and functional heterogeneity to arise among tumor cells within the same patient. This has led to increased resistance to cancer treatments and greater difficulty in predicting how a patient’s cancer will progress. To best address the relationship between cellular metabolism and tumor heterogeneity, optical imaging microscopy is employed to detect fluorescence signals of a ROS label and NADH, an important molecule in the process of cellular energy metabolism. A cyanide experiment is conducted to induce ROS in KRC cells, and ROS fluorescence assay is subsequently used to quantify ROS production. Fluorescence images of KRC cells before and after the cyanide experiment are acquired. Results demonstrate that both the optical redox ratio and ROS increased after the addition of cyanide compared to control cells without cyanide. While more experimental trials need to be conducted, current experimental outcomes relay the potential for using the relationship between NADH redox state and ROS levels to look at different phases of the cell metabolic cycle to quantify tumor heterogeneity in the future. This can help extend our understanding of the parallel between tumor treatment response and metabolically distinct tumor cell populations which is currently not well understood.
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Cellular metabolism, Optical Imaging Microscopy, Cancer, Reactive Oxygen Species, Tumor heterogeneity, Redox ratio, NADH