Cancer associated-fibroblast-derived exosomes in cancer progression

Abstract

To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

“…One of the key components that mediate intracellular communication in the tumor microenvironment is exosomes ( 31 ). For instance, it is reported that exosomes derived from melanoma cells increase the differentiation of human umbilical vein endothelial cells into cancer-associated fibroblasts, and the latter ones promote cancer progression ( 32 ). Another study discloses that exosomes derived from adenocarcinoma gastric cancer cells promote the migration and invasion of adipose-derived MSCs through transmitting circular RNA 0004303 ( 33 ).…”

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment

“…The stromal cells, particularly cancer-associated fibroblasts (CAFs), can promote tumor cell survival mainly by recruiting immune cells into the TME, and promote invasion by constructing a hypoxic environment. Tumor-driven hypoxia, increased inflammation, or MMPs overexpression in the TME induces alterations in the ECM, following the tumor biological behavior of evading apoptosis, elevating invasion and metastasis ( 17 , 18 ). In addition, ECM components can regulate the cancer-immunity cycle.…”

Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

“…It is possible that the rate of CAF-exosome secretion may also change based on ECM density/stiffness and could serve as an independent prognostic factor. The literature showing the growing number of exosomal molecules which could serve as potential biomarkers supports this hypothesis [49] .…”