肿瘤脉管系统中的一些内皮细胞表达 L 系统氨基酸转运蛋白 LAT1。为了阐明LAT1在肿瘤相关内皮细胞中的作用，将肿瘤细胞注射到内皮特异性LAT1条件性敲除小鼠（Slc7a5flox/flox；Cdh5-Cre-ERT2）中，发现肿瘤脉管系统的形状正常化，并且大小和血管结构正常化。肺转移的数量减少。在 LAT1 抑制剂 nanvuranlat 的存在下，TNFα 诱导的 HUVEC 表面 VCAM1 和 E-选择素的表达降低，这两者都负责增强单核细胞附着和转移前生态位的形成。色氨酸（一种 LAT1 底物）的剥夺模仿了 LAT1 抑制，从而导致 MEK1/2-ERK1/2 途径激活以及随后的胱硫醚 γ 裂解酶 (CTH) 诱导。 CTH 产生的硫化氢 (H2S) 增加至少在一定程度上促进了肿瘤血管正常化，从而减少了渗漏并增强了化疗药物向肿瘤的输送。

Some endothelial cells in the tumor vasculature expressed a system L amino acid transporter LAT1. To elucidate the role of LAT1 in tumor related endothelial cells, tumor cells were injected into endothelial specific LAT1 conditional knockout mice (Slc7a5flox/flox; Cdh5-Cre-ERT2) and found that the shape of the tumor vasculature was normalized and that the size and numbers of lung metastasis was reduced. TNFα-induced expression of VCAM1 and E-selectin at the surface of HUVEC, both of which are responsible for enhanced monocyte attachment and pre-metastatic niche formation, was reduced in the presence of LAT1 inhibitor, nanvuranlat. Deprivation of tryptophan, an LAT1 substrate, mimicked LAT1 inhibition, which led to activation of MEK1/2-ERK1/2 pathway and subsequent cystathionine γ lyase (CTH) induction. Increased production of hydrogen sulfide (H2S) by CTH was at least partially responsible for tumor vascular normalization, leading to decreased leakiness and enhanced delivery of chemotherapeutic agents to the tumor.