Figure 1.

Barrier function of TJs: CLDN4, which is overexpressed in epithelial malignancies, separates the intratumoral microenvironment from the tumor exterior by forming TJs. As a result, growth factors (such as EGF and VEGF) and metabolites (such as lactate) accumulate in the intratumoral microenvironment, resulting in amplification of their effects. This promotes increased tumor grade and suppression of immune cell infiltration into the tumor. TJs also inhibit the penetration of anticancer drugs from the tumor exterior into the microenvironment and enhance resistance to anticancer drugs. CLDN4, claudin-4; TJ, tight junction; EGF, epidermal growth factor; VEGF, vascular endothelial growth factor.