Figure 6.

Model of VCAM‐1/integrin mediated permeability regulation in tumor‐associated lymphatic vessels. Schematic of the proposed mechanism of how permeability and lymphatic invasion are regulated through VCAM‐1. Tumor‐derived factors, in combination with inflammatory signals from the tumor microenvironment, induce expression of VCAM‐1 and integrin α4 in associated LECs. VCAM‐1 engagement by integrin α4/β1 or α9/β1 complexes on adjacent LECs then acts on VE‐cadherin complexes in LEC junctions and induces their destabilization, possibly involving VE‐PTP detachment from VE‐cadherin. This leads to the displacement of VE‐cadherin from the junctions, increasing paracellular permeability for tissue fluid but also facilitating tumor cell invasion into the lymphatic lumen. [Color figure can be viewed at wileyonlinelibrary.com]