Stable isotope resolved metabolomics of lung cancer in a SCID mouse model

Teresa W.M. Fan; Andrew N. Lane; Richard M. Higashi; Jun Yan

doi:10.1007/s11306-010-0249-0

Stable isotope resolved metabolomics of lung cancer in a SCID mouse model

Teresa W.M. Fan, Andrew N. Lane, Richard M. Higashi, Jun Yan

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88 Scopus citations

Abstract

We have determined the time course of [U-¹³C]-glucose utilization and transformations in SCID mice via bolus injection of the tracer in the tail vein. Incorporation of ¹³C into metabolites extracted from mouse blood plasma and several tissues (lung, heart, brain, liver, kidney, and skeletal muscle) were profiled by NMR and GC-MS, which helped ascertain optimal sampling times for different target tissues. We found that the time for overall optimal ¹³C incorporation into tissue was 15-20 min but with substantial differences in ¹³C labeling patterns of various organs that reflected their specific metabolism. Using this stable isotope resolved metabolomics (SIRM) approach, we have compared the ¹³C metabolite profile of the lungs in the same mouse with or without an orthotopic lung tumor xenograft established from human PC14PE6 lung adenocarcinoma cells. The ¹³C metabolite profile shows considerable differences in [U-¹³C]-glucose transformations between the two lung tissues, demonstrating the feasibility of applying SIRM to investigate metabolic networks of human cancer xenograft in the mouse model.

Original language	English
Pages (from-to)	257-269
Number of pages	13
Journal	Metabolomics
Volume	7
Issue number	2
DOIs	https://doi.org/10.1007/s11306-010-0249-0
State	Published - Jul 2011

Bibliographical note

Funding Information:
Acknowledgments This work was supported in part by National Science Foundation EPSCoR grant # EPS-0447479, NIH Grant Number P20RR018733 from the National Center for Research Resources, 1R01CA118434-01A2 (to TWMF), R01CA-086412 and RO1 CA150947 (to JY) from the National Cancer Institute, the Kentucky Challenge for Excellence, Susan G. Komen Foundation BCTR0503648 and NCI R21CA133688 (to ANL), and the Brown Foundation. We thank J. Tan, Ruifeng Su and Mr. Richard Hansen for technical assistance. We also thank the two reviewers for many useful comments and additional references to improve the manuscript.

Funding

Acknowledgments This work was supported in part by National Science Foundation EPSCoR grant # EPS-0447479, NIH Grant Number P20RR018733 from the National Center for Research Resources, 1R01CA118434-01A2 (to TWMF), R01CA-086412 and RO1 CA150947 (to JY) from the National Cancer Institute, the Kentucky Challenge for Excellence, Susan G. Komen Foundation BCTR0503648 and NCI R21CA133688 (to ANL), and the Brown Foundation. We thank J. Tan, Ruifeng Su and Mr. Richard Hansen for technical assistance. We also thank the two reviewers for many useful comments and additional references to improve the manuscript.

Funders	Funder number
Kentucky Challenge for Excellence
National Science Foundation/EPSCoR	EPS-0447479
National Institutes of Health (NIH)	P20RR018733
National Childhood Cancer Registry – National Cancer Institute	R21CA133688
National Center for Research Resources	RO1 CA150947, 1R01CA118434-01A2, R01CA-086412
Brown Foundation
Susan G Komen Foundation	BCTR0503648

Keywords

Metabolomics
Non-small cell lung cancer xenograft
SCID mouse
SIRM
Stable isotope tracers

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Clinical Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s11306-010-0249-0

Cite this

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title = "Stable isotope resolved metabolomics of lung cancer in a SCID mouse model",

abstract = "We have determined the time course of [U-13C]-glucose utilization and transformations in SCID mice via bolus injection of the tracer in the tail vein. Incorporation of 13C into metabolites extracted from mouse blood plasma and several tissues (lung, heart, brain, liver, kidney, and skeletal muscle) were profiled by NMR and GC-MS, which helped ascertain optimal sampling times for different target tissues. We found that the time for overall optimal 13C incorporation into tissue was 15-20 min but with substantial differences in 13C labeling patterns of various organs that reflected their specific metabolism. Using this stable isotope resolved metabolomics (SIRM) approach, we have compared the 13C metabolite profile of the lungs in the same mouse with or without an orthotopic lung tumor xenograft established from human PC14PE6 lung adenocarcinoma cells. The 13C metabolite profile shows considerable differences in [U-13C]-glucose transformations between the two lung tissues, demonstrating the feasibility of applying SIRM to investigate metabolic networks of human cancer xenograft in the mouse model.",

keywords = "Metabolomics, Non-small cell lung cancer xenograft, SCID mouse, SIRM, Stable isotope tracers",

author = "Fan, {Teresa W.M.} and Lane, {Andrew N.} and Higashi, {Richard M.} and Jun Yan",

note = "Funding Information: Acknowledgments This work was supported in part by National Science Foundation EPSCoR grant # EPS-0447479, NIH Grant Number P20RR018733 from the National Center for Research Resources, 1R01CA118434-01A2 (to TWMF), R01CA-086412 and RO1 CA150947 (to JY) from the National Cancer Institute, the Kentucky Challenge for Excellence, Susan G. Komen Foundation BCTR0503648 and NCI R21CA133688 (to ANL), and the Brown Foundation. We thank J. Tan, Ruifeng Su and Mr. Richard Hansen for technical assistance. We also thank the two reviewers for many useful comments and additional references to improve the manuscript.",

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AU - Lane, Andrew N.

AU - Higashi, Richard M.

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N1 - Funding Information: Acknowledgments This work was supported in part by National Science Foundation EPSCoR grant # EPS-0447479, NIH Grant Number P20RR018733 from the National Center for Research Resources, 1R01CA118434-01A2 (to TWMF), R01CA-086412 and RO1 CA150947 (to JY) from the National Cancer Institute, the Kentucky Challenge for Excellence, Susan G. Komen Foundation BCTR0503648 and NCI R21CA133688 (to ANL), and the Brown Foundation. We thank J. Tan, Ruifeng Su and Mr. Richard Hansen for technical assistance. We also thank the two reviewers for many useful comments and additional references to improve the manuscript.

PY - 2011/7

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N2 - We have determined the time course of [U-13C]-glucose utilization and transformations in SCID mice via bolus injection of the tracer in the tail vein. Incorporation of 13C into metabolites extracted from mouse blood plasma and several tissues (lung, heart, brain, liver, kidney, and skeletal muscle) were profiled by NMR and GC-MS, which helped ascertain optimal sampling times for different target tissues. We found that the time for overall optimal 13C incorporation into tissue was 15-20 min but with substantial differences in 13C labeling patterns of various organs that reflected their specific metabolism. Using this stable isotope resolved metabolomics (SIRM) approach, we have compared the 13C metabolite profile of the lungs in the same mouse with or without an orthotopic lung tumor xenograft established from human PC14PE6 lung adenocarcinoma cells. The 13C metabolite profile shows considerable differences in [U-13C]-glucose transformations between the two lung tissues, demonstrating the feasibility of applying SIRM to investigate metabolic networks of human cancer xenograft in the mouse model.

AB - We have determined the time course of [U-13C]-glucose utilization and transformations in SCID mice via bolus injection of the tracer in the tail vein. Incorporation of 13C into metabolites extracted from mouse blood plasma and several tissues (lung, heart, brain, liver, kidney, and skeletal muscle) were profiled by NMR and GC-MS, which helped ascertain optimal sampling times for different target tissues. We found that the time for overall optimal 13C incorporation into tissue was 15-20 min but with substantial differences in 13C labeling patterns of various organs that reflected their specific metabolism. Using this stable isotope resolved metabolomics (SIRM) approach, we have compared the 13C metabolite profile of the lungs in the same mouse with or without an orthotopic lung tumor xenograft established from human PC14PE6 lung adenocarcinoma cells. The 13C metabolite profile shows considerable differences in [U-13C]-glucose transformations between the two lung tissues, demonstrating the feasibility of applying SIRM to investigate metabolic networks of human cancer xenograft in the mouse model.

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KW - Non-small cell lung cancer xenograft

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KW - SIRM

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Stable isotope resolved metabolomics of lung cancer in a SCID mouse model

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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