Section 3.3.6: Extracellular matrix and CSCs (from DOI: 10.1038/s41392-020-0110-5)

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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 3.3.6: Extracellular matrix and CSCs

The ECM is an insoluble structural component of the matrix in mesenchymal and epithelial vessels. The ECM includes collagen, elastin, aminoglycan, proteoglycan, and noncollagen glycoprotein. At present, increasing evidence shows that the ECM is an integral part of stem cell niches that regulates the balance of stem cells in three different biological states: static, self-renewal, and differentiation. Experiments in vitro and in vivo have shown that ECM receptors can be used to aggregate CSCs and induce drug resistance. Fibronectin, vimentin, collagen, and proteoglycan in the ECM bind to cytokines such as FGF, HGF, VGF, BMP, and TGF-beta in the TME and regulate their activities. In HCC, an increased matrix promotes cell proliferation and chemotherapeutic resistance and increases the expression of CSC-related markers, including CD44, CD133, c-kit, cxcr4, Oct4, and Nanog. Hyaluronic acid in the ECM is a ligand for the CD44 receptor and can regulate the acquisition and maintenance of CSC stemness during mutual contact. The ECM also binds the Wnt ligand Wnt5b via molecular MMP3 and leads to the expansion and proliferation of mammary epithelial stem cells. In addition, tenascin C in the ECM maintains the stability of breast CSCs by increasing the activity of the Wnt and Notch signaling pathways.