Section 3.3.7: Exosomes in the TME and CSCs (from DOI: 10.1038/s41392-020-0110-5)

Navigation

Article	Targeting cancer stem cell pathways for cancer therapy (DOI: 10.1038/s41392-020-0110-5)
Sections in this Publication
Section	Section 1: Introduction (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 2: The concept of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 2.1: Biological characteristics of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 2.2: Isolation and identification of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3: Factors regulating CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.1: Major transcription factors in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2: Major signaling pathways in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.1: Wnt signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.2: Notch signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.3: Hh signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.4: NF-kappaB signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.5: JAK-STAT signaling pathway (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.6: TGF/SMAD signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.7PI3K/AKT/mTOR signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.8: PPAR signaling pathways in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.9: Interactions between signaling pathways in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3: The microenvironment of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.1: Vascular niche microenvironments and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.2: The hypoxia microenvironment and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.3: Tumor-associated macrophages and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.4: Cancer-associated fibroblasts and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.5: Cancer-associated MSCs and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.6: Extracellular matrix and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.7: Exosomes in the TME and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4: Therapeutic targeting of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.1: Agents targeting CSC-associated surface biomarkers in clinical trials (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.2: Agents targeting CSC-associated signaling pathways in clinical trials (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.3: Targeting the CSC microenvironment (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.4: CSC-directed immunotherapy (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 5: Conclusions and perspectives (from DOI: 10.1038/s41392-020-0110-5)
Section	Competing interests (from DOI: 10.1038/s41392-020-0110-5)
Section	Bibliography (from DOI: 10.1038/s41392-020-0110-5)
Named Entities in this Section

From publication: "Targeting cancer stem cell pathways for cancer therapy" published as Signal Transduct Target Ther; 2020 ; 5 8; DOI: https://doi.org/10.1038/s41392-020-0110-5

Section 3.3.7: Exosomes in the TME and CSCs

Exosomes are nanovesicles secreted by various types of living cells (30-100 nm in diameter) and are widely distributed in peripheral blood, saliva, urine, ascites, pleural effusion, breast milk, and other body fluids. Exosomes contain a large number of functional proteins, RNA, microRNAs, DNA fragments, and other bioactive substances. These bioactive substances mediate material transport and information exchange between cells, thus affecting the physiological function of cells. The exosomes secreted by cancer cells promote angiogenesis, induce differentiation of tumor-related fibroblasts, participate in immune regulation of the TME, and regulate the microenvironment before metastasis. Clinical analysis has revealed that exosomes are released at higher levels in cancer cells.

Recent studies have shown that endocytosis of lipid rafts in MSCs is associated with increased secretion of exosomes. Exosome signaling mediates the interaction of CSCs and normal stem cells, thereby regulating oncogenesis and tumor development. Exosomes also regulate CSC growth by targeting specific signaling pathways, such as Wnt, Notch, Hippo, Hh, and NF-kappaB. Extracellular vesicles released by glioblastoma stem cells promote neurosphere formation, endothelial tube formation, and the invasion of glioblastoma. CSCs promote cell proliferation and self-renewal through crosstalk between exosome signal transduction and the surrounding microenvironment. The exosomes released from CSCs affect signal transduction in nearby breast cancer cells and increase the stemness of breast cancer cells. Similarly, fibroblast-derived exosomes contribute to chemoresistance by promoting colorectal CSC growth. Exosomes in the TME promote the transformation of non-CSCs into CSCs. CAF-derived exosomes significantly increase the ability to form mammary globules and promote the stemness of breast cancer cells. Similarly, CAF-derived exosomes also promote sphere formation of colorectal cancer cells by activating Wnt signaling and ultimately increase the percentage of CSCs. Exosomes from glioma-associated MSCs increase the tumorigenicity of glioma stem-like cells by transferring miR-1587. In addition, exosomes regenerate stem cell phenotypes by mediating the EMT or regulating stem cell-related signaling pathways, such as the Wnt pathway, Notch pathway, Hh pathway and other pathways, which convert cells into CSCs. Exosomes have many advantages, such as low immunogenicity, biocompatibility, easy production, cytotoxicity, easy storage, high drug loading capacity, and long life and have become ideal drug carriers for cancer therapy.