Fig. 2

Integrins that are responsible for the lung metastasis of melanoma and the inhibitors. VE-cadherin activates α2β1 integrin and the downstream signaling pathway by binding to the β1 subunit with the RGD motifs, and the activation of the α2β1 integrin pathway promotes tumor cell invasion and transendothelial migration, thus inducing lung and liver metastases. Blocking the interactions between integrin α2β1 and cadherin RGD motifs with highly selective monoclonal antibodies (mAb) significantly reduced the incidence of lung metastasis and improved the survival rate of the experimental mice. Integrins αvβ3, as a proangiogenic factor, plays an important role in directing circulating melanoma cells to the lungs and eventually leading to pulmonary metastasis by enhancing the tumor cell adherence to the pulmonary vasculature. Integrins αvβ3 inhibitors abergrin and MK-0429 selectively bind to β3 subunit and reduce the incidence of pulmonary metastasis in melanoma mouse model