Exosomes in Cancer Radioresistance.

Jie Ni,Joseph Bucci,Yong Li,David Malouf,Peter Graham,Matthew Knox

doi:10.3389/fonc.2019.00869

Jie Ni, Joseph Bucci + Show 4 more

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https://doi.org/10.3389/fonc.2019.00869

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Abstract

Radiation is a mainstay of cancer therapy. Radioresistance is a significant challenge in the treatment of locally advanced, recurrent and metastatic cancers. The mechanisms of radioresistance are complicated and still not completely understood. Exosomes are 40–150 nm vesicles released by cancer cells that contain pathogenic components, such as proteins, mRNAs, DNA fragments, non-coding RNAs, and lipids. Exosomes play a critical role in cancer progression, including cell-cell communication, tumor-stromal interactions, activation of signaling pathways, and immunomodulation. Emerging data indicate that radiation-derived exosomes increase tumor burden, decrease survival, cause radiation-induced bystander effects and promote radioresistance. In addition, radiation can change the contents of exosomes, which allows exosomes to be used as a prognostic and predictive biomarker to monitor radiation response. Therefore, understanding the roles and mechanisms of exosomes in radiation response may shed light on how exosomes play a role in radioresistance and open a new way in radiotherapy and translational medicine. In this review, we discuss recent advances in radiation-induced exosome changes in components, focus on the roles of exosome in radiation-induced bystander effect in cancer and emphasize the importance of exosomes in cancer progression and radioresistance for developing novel therapy.

Highlights

We review recent advances in the radiation-induced exosome changes, discuss the roles of exosome in radiation-induced bystander effect (RIBE) in cancer and emphasize the importance of exosomes in cancer radioresistance and progression for the development of novel therapeutic strategies
Zheng et al recently demonstrated that in lung cancer, the exosome-induced proangiogenesis effect was enhanced when the A549 and H1299 lung cancer cells were exposed to ionizing radiation (IR), and the miR23-mediated phosphatase and tensin homolog (PTEN) downregulation played an important role in this process [56]
These findings indicate that radiation-induced exosomes function as a driver of cancer progression and metastasis during RT, and may represent a putative target to improve RT strategies

Summary

Introduction

We review recent advances in the radiation-induced exosome changes, discuss the roles of exosome in radiation-induced bystander effect (RIBE) in cancer and emphasize the importance of exosomes in cancer radioresistance and progression for the development of novel therapeutic strategies. Exosomes are a major environmental factor for cellular stress, and radiation can enhance the release of exosomes and affect exosome-based intercellular communication, which has been observed in various types of normal and tumor cell lines [18, 19, 24].

Results

Conclusion