Fig. 6.

TNF-α/TNFR2-mediated invasion and metastasis in BC TME. TNFR2 signals can stimulate various proteins and signaling pathways, supporting almost all aspects of BC cell invasion and metastasis. For tumor cells to move from the primary tumor site by undergoing intravasation first and then extravasation, several enzymes, such as MMPs, must degrade the ECM. Many signaling pathways, in addition to several cytokines, chemokines, chemokine receptors, and growth factors, control the endothelial junctional proteins to induce membrane permeability. These events facilitate the movement of tumor cells, proliferation, vascularization, migration, and metastasis of BC to generate new tumors at distant sites and organs. c-DC1, type 1 conventional DCs; BC, breast cancer; BCSCs, breast cancer stem cells; MDSCs, myeloid-derived suppressor cells; T-regs, T regulatory cells; B-regs, B regulatory cells, CAFs, cancer associated fibroblast; EPCs, endothelial; MSCs, mesenchymal stem cells; TME, tumor microenvironment; ECM, extracellular matrix; MMPs, matrix metalloproteinases; iNOS, inducible nitric oxide synthase; NO, nitric oxide; TNF-α, membrane-bound tumor necrosis factor; TNFR2, tumor necrosis factor receptor type two; IL-1β, interleukin 1 beta; IL-6, interleukin 6; IL-8, interleukin 8; HIF-1α, hypoxia inducible factor 1 alpha; VEGF, vascular endothelial growth factor; pDGF, platelet-derived growth factor; IGF, insulin-like growth factor; FGF, fibroblast growth factor; HGF; CSF-1, colony stimulating factor 1; TGF-β, transforming-growth factor β; uPA, urokinase-type plasminogen; TWIST1, twist related protein-1; CCL-2, chemokine (C–C) motif ligand 2; CXCR1, C-X-C chemokine receptor 1; CXCR2, C-X-C chemokine receptor 2; CXCR-4, C-X-C chemokine receptor 4; CXCR7, C-X-C chemokine receptor 7; CCR2, C–C chemokine receptor type 2; CXCL-1, C-X-C motif chemokine ligand 1; CXCL-2, C-X-C motif chemokine ligand 2; CXCL-5, C-X-C motif chemokine ligand 5; CXCL-12, C-X-C motif chemokine ligand 12