The Role of Exosomes in Inflammatory Diseases and Tumor-Related Inflammation

Abstract

Inflammation plays a decisive role in inducing tumorigenesis, promoting tumor development, tumor invasion and migration. The interaction of cancer cells with their surrounding stromal cells and inflammatory cells further forms an inflammatory tumor microenvironment (TME). The large number of cells present within the TME, such as mesenchymal stem cells (MSCs), macrophages, neutrophils, etc., play different roles in the changing TME. Exosomes, extracellular vesicles released by various types of cells, participate in a variety of inflammatory diseases and tumor-related inflammation. As an important communication medium between cells, exosomes continuously regulate the inflammatory microenvironment. In this review, we focused on the role of exosomes in inflammatory diseases and tumor-related inflammation. In addition, we also summarized the functions of exosomes released by various cells in inflammatory diseases and in the TME during the transformation of inflammatory diseases to tumors. We discussed in depth the potential of exosomes as targets and tools to treat inflammatory diseases and tumor-related inflammation.

Keywords: exosomes; inflammatory disease; tumor microenvironment; tumor-related inflammation.

Figure 1

The role of exosomes in inflammatory diseases and tumor-related inflammation. (a) During sepsis, exosomes released by donor cells contain large amounts of inflammatory factors (TNF-α, IL-6, IL-10) and DAMP molecules, which lead to the activation of downstream inflammatory signaling pathways. (b) Exosomes lead to COPD, ALI/ARDS, ASTHMA and other pulmonary inflammatory diseases by encapsulating different molecules, such as IL-8, caspase-1, MHCII, ICAM-1, and may further promote cell proliferation, EMT and angiogenesis to promote the development of lung cancer. (c) DAMP molecules encapsulated by exosomes cause severe inflammatory responses in the liver. Exosomes derived from different donor cells also promote or inhibit the occurrence of viral hepatitis through different mechanisms. In addition, exosome-encapsulated miRNA-128-3p promote liver fibrosis by inhibiting PPAR-γ. Of course, exosomes also play an important role in the occurrence and development of liver cancer. (d) In intestinal inflammation, exosomes not only contain many inflammatory factors, but also induce the polarization of macrophages to TAM, both of which further lead to the occurrence and development of CRC. DAMP, damage-associated molecular pattern; COPD, chronic obstructive pulmonary disease; ALI/ARDS, acute lung injury/acute respiratory distress syndrome; EMT, epithelial-mesenchymal transition; TAM, tumor-associated macrophage; CRC, colitis-associated colorectal cancer.

Figure 2

Tumor-derived exosomes promote tumor development. Tumor-derived exosomes contribute to the development of tumors via promoting tumor cell proliferation (a), regulating immune responses (b), enhancing epithelial-mesenchymal transition (EMT) (c) and angiogenesis (d), and strengthening tumor metastasis (e).