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13C Tracer Studies of Metabolism in Mouse Tumor Xenografts
Andrew N Lane1, Jun Yan2, Teresa W-M Fan1
1Center for Environmental Systems Biochemistry, Dept. Toxicology and Cancer Biology and Markey Cancer Center, Lexington, USA.
Abstract:
Mice are widely used for human tumor xenograft studies of cancer development and drug efficacy and toxicity. Stable isotope tracing coupled with metabolomic analysis is an emerging approach for assaying metabolic network activity. In mouse models there are several routes of tracer introduction, which have particular advantages and disadvantages that depend on the model and the questions addressed. This protocol describes the bolus i.v. route via repeated tail vein injections of solutions of stable isotope enriched tracers including 13C6-glucose and 13C5,15N2-glutamine. Repeated injections give higher enrichments and over longer labeling periods than a single bolus. Multiple injections of glutamine are necessary to achieve adequate enrichment in engrafted tumors.
Insights
This study details a method for tracking cancer metabolism in mice using stable isotope tracers. Repeated intravenous injections of labeled glucose and glutamine improve metabolic network analysis in tumor xenografts.
Area of Science:
- Biomedical research
- Metabolomics
- Cancer research
Background:
- Mice are crucial models for human cancer xenograft studies.
- Stable isotope tracing combined with metabolomics offers insights into metabolic network activity.
- Various tracer administration routes exist, each with specific pros and cons.
Purpose of the Study:
- To describe a protocol for stable isotope tracer administration in mouse xenograft models.
- To optimize tracer enrichment and labeling duration for enhanced metabolic analysis.
- To establish a reliable method for studying cancer metabolism and drug responses.
Main Methods:
- Utilizing the bolus intravenous (i.v.) route for tracer delivery.
- Administering repeated tail vein injections of stable isotope-enriched tracers.
- Employing 13C6-glucose and 13C5,15N2-glutamine as tracers.
Main Results:
- Repeated injections achieve higher tracer enrichment compared to single bolus administration.
- Extended labeling periods are feasible with the described injection protocol.
- Multiple glutamine injections are essential for sufficient enrichment in engrafted tumors.
Conclusions:
- The described i.v. bolus injection protocol enhances stable isotope tracing in mouse xenograft models.
- This method provides a robust approach for investigating cancer metabolism and evaluating drug efficacy.
- Optimized tracer administration is key for accurate metabolomic analysis in cancer research.
