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Review
. 2022 Jun 28;15(1):83.
doi: 10.1186/s13045-022-01305-4.

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Mahshid Deldar Abad Paskeh #  1   2 , Maliheh Entezari #  1   2 , Sepideh Mirzaei #  3 , Amirhossein Zabolian  4 , Hossein Saleki  4 , Mohamad Javad Naghdi  4 , Sina Sabet  4 , Mohammad Amin Khoshbakht  4 , Mehrdad Hashemi  1   2 , Kiavash Hushmandi  5 , Gautam Sethi  6   7 , Ali Zarrabi  8 , Alan Prem Kumar  6   7 , Shing Cheng Tan  9 , Marios Papadakis  10 , Athanasios Alexiou  11   12 , Md Asiful Islam  13   14 , Ebrahim Mostafavi  15   16 , Milad Ashrafizadeh  17
Affiliations
Review

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Mahshid Deldar Abad Paskeh et al. J Hematol Oncol. .

Abstract

Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment.

Keywords: Biomarker; Cancer; Exosome; Immunotherapy; Non-coding RNA; Prognosis.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1
Fig. 1
The biogenesis of exosomes. Exosomes contain various types of cargoes such as siRNA, circRNA, lncRNA, mRNA, miRNA, lipids, and proteins, and are therefore involved in various biological mechanisms in cells. They have a particle size of 30–150 nm and various types of proteins shown in the figure may be involved in the biogenesis of exosomes. Targeting these proteins may regulate exosome biogenesis and provide new insights for the development of therapeutics
Fig. 2
Fig. 2
Exosomes in the regulation of the TME. Proliferation and metastasis of tumor cells are strongly modulated by the TME. Exosomes can influence various cellular interactions in the TME and affect tumor progression. In addition, exosomes can transport both anti-tumor agents (oxaliplatin) and siRNA into the TME and modulate tumor growth
Fig. 3
Fig. 3
Exosomes in the modulation of angiogenesis in cancer cells. The molecular signaling pathways that regulate angiogenesis, including Akt, PTEN, β-catenin, TSGA10, and ANGPT2, are regulated by exosomes. Induction of angiogenesis promotes tumor progression and therapeutic targeting of exosomes may impair cancer growth
Fig. 4
Fig. 4
Exosomes in the regulation of cancer cell growth and invasion. Glycolysis responsible for tumor growth is regulated by exosomes. CAFs are able to secrete exosomes to modulate tumor progression. EMT, metastasis, ROS and apoptosis are other signaling pathways affected by exosomes in tumor cells
Fig. 5
Fig. 5
The role of exosomes in modulating the response to drug therapy. Most experiments focused on exosomal miRNAs and their downstream targets such as PTEN and JAK2. PTEN suppresses cancer progression, while JAK2 promotes cancer malignancy. Depending on the function of each molecular mechanism, the role of exosomes in cancer progression or inhibition varies
Fig. 6
Fig. 6
The exosomal ncRNAs in modulating cancer progression. A variety of signaling networks are influenced by exosomal ncRNAs. Metastasis, growth, apoptosis and response to therapy are strongly modulated by exosomal ncRNAs. Further experiments are needed to identify other exosomal circRNAs, as studies have focused more on exosomal miRNAs and lncRNAs
Fig. 7
Fig. 7
The use of exosomes in the administration of genetic tools. Downregulation of tumor-promoting molecular signaling pathways such as survivin, Bcl-2, PLK1, HGF, and TPD52 by exosomes loaded with genetic tools leads to induction of apoptosis, impairment of tumor progression, and suppression of cancer metastasis
Fig. 8
Fig. 8
Tumor-derived exosomes and their role in cancer progression
See this image and copyright information in PMC

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