Molecular mechanism of therapeutic approaches for human gastric cancer stem cells

Figure 2 The roles of gastric cancer stem cells in the tumor microenvironment and activated in gastric cancer stem cells. This figure shows the dynamic regulation of the tumor niche and GCSCs. Cancer cells (non-CSCs) can dedifferentiate by regulating their intracellular signaling pathways, gene expression, and epigenetic modification through the functional connection of the tumor niche to differentiated cancer cells (non-CSCs) to obtain the GCSC phenotype. Stromal cells can support GCSCs development through various kinds of interactions. Tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), tumor vascular endothelial cells (ECs) and hypoxia not only directly enhance the CSC capabilities of GCSCs by activating the several pathways but also inhibit T cells and dendritic cells (DCs) activity. TGF-β: transforming growth factor-β; SDF-1α: stromal cell-derived factor-1α; PD-1: programmed cell death 1; PD-L1: programmed cell death 1 Ligand 1; CD133: cluster of differentiation 133; MFG-E8: milk fat globule epidermal growth factor 8; NO: nitric oxide; eNOS: endothelial NO·synthase; IL-6: interleukin 6; MCP1: monocyte chemoattractant protein 1; VEGF: vascular endothelial growth factor.