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Tracking the Metabolic Fates of $^{\mathrm{13}}$C and $^{\mathrm{15}}$N-alanine in Glioblastoma

ORAL

Abstract

Glioblastoma is one of the most lethal forms of cancer with a very dismal survival rate. Such tumors are mostly chemoresistant and difficult to detect at an early stage. Thus, there is an unmet clinical need of non-invasive methods for early detection of glioblastoma. In this study, we have investigated the metabolism of $^{\mathrm{13}}$C,$^{\mathrm{15}}$N-labeled alanine in SfXL glioblastoma cells with different incubation times of the substrate using NMR spectroscopy. Our data show high production of $^{\mathrm{13}}$C-lactate from $^{\mathrm{13}}$C-alanine and that the intermediate metabolite $^{\mathrm{13}}$C-pyruvate was not visible in the $^{\mathrm{13}}$C NMR spectra up to 48 hours of incubation time. Consequently, we also track the metabolic fate of $^{\mathrm{15}}$N-amino arm of alanine to complete the metabolic story of this amino acid in cancer. These results suggest that glioblastoma cells prefer rapid lactic acid production from alanine-derived pyruvate, indicative of the hyperactive ALT and LDH activities in these cells. This study is supported by Welch grant AT-1877-20180324, DOD grants W18XWH-17-1-0303 and DOD W81XWH-19-1-0741, CPRIT grant RP180716, and the UTD Collaborative Biomedical Research Award (CoBRA).

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Authors

  • Qing Wang

    University of Texas at Dallas, the University of Texas at Dallas

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory

  • Eric Davis

    University of Texas at Arlington, Sultan Qaboos University, UTA HEP group, Department of Integrated Bio \& Nano Systems, University of Houston, Houston, TX 77204, USA, Department of Electrical and Computer Engineering, Nano Tech Center, Texas Tech University, University of Michigan, University of Waerloo, Canada, Texas Tech University, Dept of Mechanical Eng, TTU; Dept. of Physics and Astronomy, TTU, Dept of Cell Biology and Biochemistry, TTU Health Sci Ctr, Dept of Physics and Astronomy, TTU, Dept of Mechanical Engineering, TTU, Dept of Physics and Astronomy, TTU; Sch of Health and Sci, Purdue Univ, Dept of Mathematical and Systems Engineering, Shizuoka Univ, Department of Physics, University of Texas at Dallas, Richardson, TX 75080, Department of Physics, University of Texas at Dallas, Richardson, TX 75080., LeTourneau University, None, University of Waterloo, Canada, Texas Tech Univ, Trinity University, the University of Texas at Dallas, Texas Tech University, Lubbock, TX, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada, University of Dallas, Liverpool John Moores University, University Of Houston, Biolog Department, TCU, Home Schooled high school student, Los Alamos National Laboratory