Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression

Because lymphatic vessels (LVs) play critical roles not only in physiological processes such as maintenance of fluid homeostasis but also in pathological conditions including cancer metastasis, identification of factors that control LV formation is crucial. Signals mediated by activin receptor-like kinase 1 (ALK-1), a receptor for bone morphogenetic protein 9 (BMP-9), have been implicated in the formation of blood vessels because of its linkage to a human vascular disease. However, their roles in LV formation largely remain to be elucidated. Here, we show that BMP-9/ALK-1 signals inhibit LV formation in physiological and pathological conditions. Furthermore, we elucidated its molecular mechanisms in detail, using both in vivo and in vitro systems. These findings will help develop therapeutic strategies for LV-related diseases such as lymphedema and cancer.