We propose a novel mechanism by which AMIGO2-expressing cancer cells within tumor tissues stimulate endothelial cells in target organs for enabling the establishment of pre-metastatic niches via the effect of AMIGO2-containing EVs, which enhance the adhesion of endothelial cells to not only AMIGO2-positive but also AMIGO2-negative cancer cells (Fig. 4c,d). Here, AMIGO2 is linked to cancer.