Angiopoietins and TIE receptors in lymphangiogenesis and tumor metastasis

Abstract

In contrast to the normal lymphatic network comprised of initial and collecting vessels, intratumor lymphatics are disorganized and lack vessel hierarchy due to the continuous lymphangiogenesis. Lymphatic vessels originate from veins during mammalian development, while tumor-associated lymphatics are largely formed by vessel cooption or sprouting from the preexisting lymphatics of adjacent tissues. Among the known lymphangiogenic regulators, angiopoietins and TIE receptors are crucial for the process of lymphatic remodeling to form a mature network. Accumulating evidence from animal and clinical studies has laid a solid foundation that tumor lymphangiogenesis contributes to tumor dissemination. It has been shown in animal tumor models that targeting the key lymphangiogenic signaling pathways, including ANGPT-TIE mediated signals, could efficiently block lymphatic tumor metastasis. Meanwhile, ANGPT-TIE pathway is also actively involved in modulating tumor immune microenvironment. Therefore, strategies to fine-tune the interaction of lymphatic EC-immune cells could be employed in the prevention of tumor progression.