Biofluorescence imaging-guided spatial metabolic tracing: In vivo tracking of metabolic activity in circulating tumor cell-mediated multi-organ metastases

Hemi Luan ¹, Shuailong Chen ², Jingru Lian ³

¹Department of Biomedical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China; Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang, 515200, China; State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.
²School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
³Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
⁴Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
⁵Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang, 515200, China; School of Environmental and Chemical Engineering, Wuyi University, Jiangmen, 529020, China.
⁶Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China; Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen, 518055, China.

⁰Department of Biomedical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China; Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang, 515200, China; State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.

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August 13, 2024

View abstract on PubMed

Summary

Metabolic reprogramming in circulating tumor cells (CTCs) drives metastasis. Our new Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT) reveals metabolic heterogeneity in CTCs, offering new therapeutic targets.

Area Of Science

Oncology
Metabolomics
Molecular Biology

Background

Circulating tumor cells (CTCs) are key drivers of cancer metastasis.
Metabolic reprogramming is crucial for metastatic progression.
Current methods for studying metabolic heterogeneity in metastases are limited.

Purpose Of The Study

To develop a novel technology for evaluating in vivo metabolic heterogeneity within organ-specific metastases.
To investigate the metabolic landscape of CTC-mediated metastasis.

Main Methods

Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT) integrates in vivo biofluorescence imaging, stable isotope tracing, stain-free laser capture microdissection, and liquid chromatography-mass spectrometry.
The method enhances detection sensitivity and accuracy by chemically derivatizing polar metabolites in central carbon pathways.
BIGSMT obviates the need for staining or intricate sample preparation, minimizing metabolite loss.

Main Results

BIGSMT revealed significant heterogeneity in glucose carbon flux into glycolysis and the TCA cycle across distinct metastatic sites in a preclinical CTC-mediated metastasis model.
Metabolic analysis indicated that pyruvate dehydrogenase is the primary enzyme responsible for carbon entry into the TCA cycle.
The study identified site-specific metabolic differences in melanoma CTC metastasis.

Conclusions

BIGSMT provides unprecedented spatial resolution for metabolic profiling of metastases in vivo.
The findings offer new insights into the metabolic heterogeneity and evolution of CTC-mediated metastasis.
This technology highlights potential novel therapeutic strategies targeting metabolic pathways in metastatic cancer.

Keywords:

Biofluorescence imaging-guided spatial metabolic tracing (BIGSMT) Circulating tumor cell (CTC) Liquid chromatography-mass spectrometry (LC-MS) Melanoma metastasis Metabolic reprogramming