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Updated: Jul 26, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

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Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their

Muireann Ní Bhaoighill1,2, Juan M Falcón-Pérez3,4,5, Félix Royo3,4

  • 1Tissue Microenvironment Group, School of Medicine, Cardiff University, Cardiff, UK.

Journal of Extracellular Vesicles
|June 20, 2023
PubMed

Insights

Extracellular vesicles (EVs) from Tuberous Sclerosis Complex (TSC) cells promote tumor growth. Rapamycin therapy alters these EVs, offering a new therapeutic avenue and potential biomarkers for TSC.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) drives many solid tumors and Tuberous Sclerosis Complex (TSC).
  • Extracellular vesicles (EVs) modulate the tumor microenvironment, but their role in TSC tumorigenesis is unclear.

Purpose of the Study:

  • To investigate the contribution of EVs to tumor growth in TSC.
  • To characterize EVs secreted from TSC2-deficient and TSC2-expressing cells.
  • To explore the therapeutic effects of rapamycin on EVs in TSC.

Main Methods:

  • Characterization of EVs from TSC2-deficient and TSC2-expressing cells.
  • Analysis of protein cargo within EVs.
  • Assessment of EV effects on fibroblast viability, proliferation, and growth factor secretion.
  • Evaluation of rapamycin's impact on EV cargo and function.
  • Identification of potential plasma biomarkers in TSC patients.

Main Results:

  • TSC2-deficient EVs exhibit distinct protein cargo enriched in tumor-promoting pathways.
  • EVs from TSC2-deficient cells enhance recipient fibroblast viability, proliferation, and growth factor secretion.
  • Rapamycin treatment alters EV cargo and reduces their tumor-promoting capacity.
  • Three EV-associated proteins are elevated in plasma from TSC patients, suggesting biomarker potential.

Conclusions:

  • EVs play a significant role in promoting tumor growth within the TSC tumor microenvironment.
  • Rapamycin exhibits an intercellular therapeutic effect by modifying EVs.
  • EV-associated proteins represent promising biomarkers for TSC diagnosis and monitoring.
Keywords:
TSC2extracellular vesicles (EVs)fibroblastsmTORC1tuberous sclerosis complex (TSC)tumour microenvironment

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