Extracellular vesicle DNA regulates immune responses and suppresses liver metastasis

 

In a recent study published in Nature Cancer, a team of researchers investigated the unique structure of deoxyribonucleic acid (DNA) in extracellular vesicles (EVs) and its role in cancer progression.

The study examined how EV-DNA, through its association with histones, influences immune cell responses and impacts the pre-metastatic niche. It also explored how it could serve as a predictive biomarker for metastasis, especially in colorectal cancer.

Background

Extracellular vesicles are nano-sized structures secreted by cells to mediate communication, especially in disease contexts such as cancer.

These vesicles carry diverse molecular particles, including DNA, proteins, and ribonucleic acid (RNA). Previous research has shown that EVs are involved in preparing distant organs for tumor colonization by forming pre-metastatic niches.

However, while many of the proteins and RNA in EVs have been linked to tumor progression, the role of EV-DNA remains less clear.

About the study

As genomic DNA constitutes a significant fraction of EV-DNA, it presents a potential marker for tumor-specific mutations. The gap in knowledge about the functions and mechanisms of EV-DNA in cancer also necessitates further research to understand its influence on cancer metastasis and immune regulation, as well as its potential clinical applications.

The present study employed a combination of cellular, molecular, and in vivo techniques to investigate the role of EV-DNA in cancer progression. Using ultracentrifugation, extracellular vesicles were isolated from various cancer cell lines, including colorectal and breast cancer models.

Major findings

The findings suggested that EV-DNA has a critical role in inhibiting metastasis through immune activation. The researchers identified the primarily genomic and chromatinized EV-DNA as a key trigger for immune responses when taken up by liver macrophages or Kupffer cells.

After taking up EV-DNA, these cells exhibited activation of DNA damage response pathways, leading to the production of cytokines that promote antitumor immunity.

Conclusions

Overall, the study established EV-DNA as an important factor in activating immune defenses against metastasis and highlighted its unique chromatin structure. The findings demonstrated that EV-DNA levels are inversely correlated with metastatic potential, offering a promising biomarker for assessing cancer prognosis.

By elucidating the mechanisms of EV-DNA’s impact on immune activation and metastasis, the study paved the way for innovative therapeutic strategies targeting EVs in cancer treatment.

website: popularscientist.com

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