Kinetic Analysis of Lipid Metabolism in Breast Cancer Cells via Nonlinear Optical Microscopy.

ABSTRACT

Investigating the behavior of breast cancer cells via reaction kinetics may help unravel the mechanisms that underlie metabolic changes in tumors. However, obtaining human in vivo kinetic data is challenging because of difficulties associated with measuring these parameters. Nondestructive methods of measuring lipid content in live cells provide a novel approach to quantitatively model lipid synthesis and consumption. In this study, coherent Raman scattering microscopy was used to probe de novo intracellular lipid content. Combining nonlinear optical microscopy and Michaelis-Menten kinetics-based simulations, we isolated fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells. When treated with 17ß-estradiol, the lipid utilization in cancer cells jumped by twofold. Meanwhile, the rate of de novo lipid synthesis in cancer cells treated with 17ß-estradiol was increased by 42%. To test the model in extreme metabolic conditions, we treated T47D cells with etomoxir. Our kinetic analysis demonstrated that the rate of key enzymatic reactions dropped by 75%. These results underline the capability to probe lipid alterations in live cells with minimum interruption and to characterize lipid metabolism in breast cancer cells via quantitative kinetic models and parameters.