Angiogenesis, a process of vascular growth from preexisting vessels, is involved in pathological processes including tumor growth and metastasis. L-type amino acid transporter 1 (LAT1) is highly expressed in a wide range of cancers and contributes to supplying amino acids. LAT1 has, thus, been proposed as a potential target for cancer therapy. Recently, we found that LAT1 shows high expression not only in tumor cells but also in endothelial cells of pancreatic cancer tissues. In contrast, the expression of LAT1 in endothelial cells of normal tissues is limited. In this study, we examined whether LAT1 is involved in tumor angiogenesis or not. LAT1 inhibitors reduced the number of blood vessel sprouting in ex vivo aortic ring assay. Suppression of angiogenesis by LAT1 inhibitors was further confirmed in in vivo matrigel plug assay and xenograft tumor model. Moreover, contribution of LAT1 in angiogenesis was verified using human umbilical vein endothelial cells in in vitro angiogenesis assays. LAT1 inhibitors are supposed to exert an anti-angiogenic effect through the inhibition of LAT1 in the endothelial cells of tumors, which could, together with the suppression of amino acid uptake of cancer cells, contribute to the anti-tumor effect in vivo.

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