Fig. 1

Integrin that is responsible for lymph node metastasis in melanoma and its inhibitors. Integrin α4, especially α4β1 isoform, promotes the adhesion of melanoma cells to the lymphatic endothelial cells (LECs) via binding to VCAM-1. α4β1⁺ melanoma cells tend to adhere to VCAM-1⁺ LECs, and α4β1⁺ LECs have high affinity to VCAM-1⁺ melanoma cells as well. The lymphangiogenic growth factor VEGF-C, which is secreted by tumor cells and transported to ECM, is supposed to induce the expression and activation of integrin α4β1 on LECs. Monoclonal antibody natalizumab and small molecules TBC3486 and JK273 are inhibitors of integrin α4β1