ADAMTS1 metalloproteinase inhibits lymphangiogenesis and mechanobiology of lymphangiogenesis

ADAMTS 1是一种基质金属蛋白酶，抑制血管生成。我们研究了ADAMTS 1对淋巴管生成的影响。我们进一步研究了肿瘤间质液压力（TIFP）和肿瘤生长之间的关系。我们证明过表达的ADAMTS 1转染子与VEGFC结合并形成复合物并抑制VEGFR 3的磷酸化，从而抑制淋巴管生成。此外，当在异种移植小鼠模型中注射VEGFC以增强淋巴管生成时，TIFP减少并且肿瘤生长也减弱。最后，我们延伸HMVEC-dLys并检测淋巴管生成相关基因。机械应力可能参与调节淋巴管内皮细胞淋巴管生成相关基因的表达。

ADAMTS1 is a matrix metalloproteinase and inhibits angiogenesis. We investigated the effect of ADAMTS1 on lymphangiogenesis. We further examined the relationship between tumor interstitial fluid pressure (TIFP) and tumor growth. We demonstrated that overexpressed-ADAMTS1 transfectants bind to VEGFC and made a complex and dampened the phosphorylation of VEGFR3, inhibiting lymphangiogenesis. Moreover, when VEGFC was injected to enhance lymphangiogenesis in a xenograft mouse model, TIFP was reduced and tumor growth was also attenuated. Finally, we stretched HMVEC-dLys and examined lymphangiogenesis-related genes. Mechanical stress may be involved in the regulation of lymphangiogenesis-related gene expressions in lymphatic endothelial cells.