Fig. 4
From: Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
Regulation of ECM stiffness on Angiogenesis, Drug Resistance, Immune Escape and Metabolic Reprogramming. a. ECM stiffness supports the growth and survival of ECs mainly by enhancing the expression of VEGF and its receptors; On the contrary, ECM stiffness can also act as a barrier to ECs migration, and ECM protein fragmentation can also act as an anti-angiogenic agent. b. Matrix stiffness actively removes chemotherapeutic drugs from cancer cells by enhancing the functional activity of MRP1, ABC transporters on the cell membrane, and also acts as a barrier to block drug delivery c. EC stiffness not only acts as a physical barrier to block the infiltration of immune cells into the TME, but also limits the contact of anti-apcs with T cells and regulates the polarization of macrophages. d. Matrix stiffness regulates glycolysis, amino acid metabolism, and lipid metabolism in tumors through multiple mechanisms