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. 2022 Jun 1;9:918789. doi: 10.3389/fmolb.2022.918789

FIGURE 2.

FIGURE 2

MMPs and the metastatic cascade. During cancer progression, MMPs have a relevant role in each step until they form a new colony in a distant organ. They participate in the remodeling of the ECM and cancer cells’ migration until they reach blood or lymphatic vessels. MMPs are involved in angiogenesis, including the activation of TECs and lymphangiogenesis (MMP-2, MMP-3, MMP-9, MMP-13, MMP-14, and MMP-16, not shown in the figure). MMPs contribute to the intravasation and protect neoplastic cells from immune response and shear stress from the bloodstream. MMPs are also implicated in the extravasation and formation of the metastatic niche. Adapted with permission from Gonzalez-Avila G., Sommer, B., Mendoza-Posada, D.A., Ramos, C., Garcia-Hernandez, A.A., and Falfan-Valencia, R. (2019). Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit. Rev. Oncology/Hematology 137, 57–83. doi: 10.1016/j.critrevonc.2019.02.010. Copyright 2021. Abbreviations: CAF, cancer associate fibroblast; CSC, cancer stem cell; ECM, extracellular matrix; MMP, matrix metalloproteinase; NK, natural killer; TAM, tumor associate macrophage, TAN, tumor associated neutrophil; TEC, tumor endothelial cell.