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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation:
Sergey Leonov1,2, Anna Dorfman1, Elizaveta Pershikova1
1Department of Cell Technologies, Institute of Future Biophysics, 141700 Dolgoprudny, Russia.
Abstract:
During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.
Insights
Extracellular vesicles (EVs) transfer mitochondria in non-small cell lung cancer (NSCLC), influencing cell behavior and radiation response. This review explores the controversy and potential new radiation therapies.
Area of Science:
- Cell Biology
- Cancer Research
- Oncology
Background:
- Extracellular vesicles (EVs) mediate intercellular cargo transfer, influencing recipient cell functions like proliferation and apoptosis.
- Metastatic cancer cells utilize EVs to remodel the tumor microenvironment (TME), promoting invasion and metastasis.
- Intercellular transfer of mitochondria, including mitochondrial DNA (mtDNA) and RNA (mtRNA), via EVs and tunneling nanotubes (TNTs) is observed in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To review the current understanding of EV-mediated mitochondrial transfer in NSCLC.
- To highlight the controversy surrounding the impact of mitochondria transfer on cancer progression and radiation response.
- To discuss novel radiation therapy approaches that may overcome cancer resistance mechanisms.
Main Methods:
- Literature review of studies investigating EVs, mitochondria transfer, and radiation response in NSCLC.
- Analysis of experimental data on the mechanisms of mitochondrial transfer (EVs, TNTs).
- Exploration of emerging radiation therapy modalities.
Main Results:
- EVs can transfer intact mitochondria organelles (MtO), mtDNA, and mitochondrial signatures (MtS) in NSCLC.
- Cancer cells can acquire mitochondria from TME cells via TNTs, potentially restoring metabolic function.
- The role of mitochondria transfer in modulating NSCLC radiation sensitivity remains debated, with conflicting evidence.
Conclusions:
- EV-mediated mitochondrial transfer is a complex process in NSCLC with implications for tumor behavior.
- Understanding mitochondria transfer mechanisms is crucial for deciphering cancer resistance to therapy.
- New radiation strategies are needed to address mitochondria-driven resistance in NSCLC.
