Title : The role of Angiopoietin-2 (Ang2) in lymphangiogenesis and the tumor microenvironment
Abstract:
Lymphangiogenesis is an essential physiological process but also a determining factor in vascular-related pathological conditions. Angiopoietin-2 (Ang2) plays an important role in lymphatic vascular development and function and its upregulation has been reported in several vascular-related diseases, including cancer. Here, we show that Ang2-driven human dermal lymphatic endothelial cell migration depends on the small GTPase RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on β1 integrin-mediated RhoA activation and we dissected the downstream signaling pathway. The Ang2-RhoA relationship was explored in vivo, where lymphatic endothelial RhoA deficiency blocked Ang2-induced lymphangiogenesis, highlighting RhoA as an important target for anti-lymphangiogenic treatments. To evaluate the role of tumor-derived Ang2 on tumor formation, we knocked down Ang2 expression in tumor cells with CRISPR-CAS editing and evaluated the impact of its deficiency on tumor cell functions, tumor growth and tumor microenvironment characteristics.
