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. 2020 Jul 23;8:748. doi: 10.3389/fbioe.2020.00748

FIGURE 2.

FIGURE 2

Mesenchymal stem cell characteristics and activities in tumor suppression. (1) Mesenchymal stem cells express several surface molecules that have a pivotal role in their homing to tumor sites. These surface molecules are important during MSC adhesion to different cell types; for example, MSCs express connexin 43 on their membrane, which plays an important role in MSC adhesion to endothelial cells. (2) Tumor cells are able to produce several growth factors, for example, vascular endothelial growth factor, which stimulates new vessel formation and angiogenesis. Mesenchymal stem cells inhibit tumor angiogenesis by reducing the secretion of these growth factors and inducing apoptosis and/or cell cycle arrest in endothelial cells. (3) During and after tumor formation, tumor cells undergo uncontrolled proliferation. Mesenchymal stem cells inhibit tumor cell proliferation by decreasing the expression of positive regulators of cell cycle and/or regulating cell cycle inhibitory genes. (4) Mesenchymal stem cells can increase tumor cell apoptosis either by up-regulating death receptors expression (extrinsic pathway of apoptosis) or stimulating intrinsic pathway of apoptosis. (5) Mesenchymal stem cells inhibit tumor metastasis by decreasing tumor cell motility in the primary site of a tumor. (6) Decreasing permeability of lymphatic or blood vessels for circulating tumor cells. (7) Early after carcinogen exposure, the initial inflammatory response is started, which recruits other innate immune cells from nearby capillaries. Mesenchymal stem cells affect different types of immune cells in the site of inflammation and modulate the immune response, which results in tumor inhibition. Mesenchymal stem cells decrease the amount of M2 phenotype macrophages (which promote tumor tolerance and angiogenesis through secretion of VEGF, TGF-β, and other soluble factors) and induce more regulatory T cells (which are produced during the active phase of immune response and limit the strong immune response by CD4+ and CD8+ cells and as a result prevent damage to the host tissue) to enter the inflammatory site.