In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues

EMBO Mol Med, 2022 · DOI: 10.15252/emmm.202216029 · Published: September 5, 2022

Simple Explanation

This research introduces a new method using mass spectrometry imaging to map glycogen distribution in tissues. The study reveals that glycogen stores vary significantly between different tissues and within different regions of the same tissue, both in healthy and cancerous samples. The findings suggest that targeting glycogen metabolism could be a potential therapeutic strategy, particularly in Ewing sarcoma, a pediatric bone cancer.

Study Duration

Not specified

Participants

Human and mouse tissues

Evidence Level

Not specified

Key Findings

1
Glycogen distribution is heterogeneous among different tissues and within different regions of the same tissue in both mice and humans.
2
Ewing sarcoma exhibits high levels of glycogen with a unique architecture characterized by hyperphosphorylation, resembling glycogen storage diseases.
3
Targeting glycogen synthesis or glycogen hyperphosphorylation in Ewing sarcoma preclinical models inhibits tumor growth in vivo.

Research Summary

This study introduces a new MALDI-MSI workflow for in situ imaging of glycogen, providing spatial quantification of glycogen levels and architecture in tissues. The method reveals heterogeneous glycogen distribution in various mouse and human organs, as well as in different cancer types, highlighting the unique glycogen accumulation in Ewing sarcoma (ES). Targeting ES glycogen through genetic and pharmacological methods inhibits tumor growth in vivo, suggesting a novel therapeutic target.

Practical Implications

Therapeutic Target Identification

The study identifies glycogen metabolism as a potential therapeutic target for Ewing sarcoma, offering new avenues for drug discovery.

Diagnostic Tool Enhancement

The MALDI-MSI workflow provides a sensitive method for characterizing glycogen structure and distribution, which can be used to diagnose and monitor glycogen-related diseases.

Personalized Medicine

Understanding the heterogeneous distribution of glycogen in different tissues and cancers can lead to more personalized treatment approaches.

Study Limitations

1
Glycogenolysis postmortem may affect spatial glycogen distribution; therefore, rapid dissection and tissue fixation following euthanasia are critical.
2
The laser spot size of 50 μm may limit single-cell analysis, although newer MALDI-MSI mass spectrometers with 5 μm resolution would allow near single-cell analysis.
3
Additional work is needed to rigorously identify classes of tumors that will respond to therapeutic agents targeting glycogen.

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