Lymphatic endothelial tumors induced by intraperitoneal injection of incomplete Freund's adjuvant

Endothelial cells form the inner lining of blood and lymphatic vessels. In mice, only tumors of the blood vessel endothelium (haemangiomas) have been thus far reported. Here we describe a highly reproducible method for the in duction of benign tumors of the lymphatic endothelial cells (lymphangiomas) in mice by intraperitoneal injection of incomplete Freund's adjuvant, Morp hological and histopathological studies of the lesions revealed the presenc e of cells at various levels of vascular development. The lymphangiomas dev eloped in the peritoneal cavity and expressed the endothelial markers CD31/ PECAM (platelet endothelial cell adhesion molecule), CD54/ICAM-1 (InterCell ular Adhesion Molecule-1), and CD102/ICAM-2, as well as the vascular endoth elial growth factor (VEGF) receptor Flk-1, the endothelial cell specific re ceptors Tie-1 and Tie-a and the lymphatic endothelial cell specific Flt4 re ceptor as shown by in situ hybridization, The Flk-1 and Flt4 receptors were also identified in immunoblots of the tumors and in cells cultured from th em. When induced in beta-galactosidase knock-in Flt4(+/-) mice, the tumor e ndothelia could be stained blue in a number of tumor cells although the sta ining was of lower intensity than in normal lymphatic vessels. The tumor-de rived cells could be propagated in vitro and they spontaneously differentia ted, forming vessel-like structures, Murine lymphangiomas thus represent a highly reproducible and convenient source of lymphatic endothelial cells. ( C) 1999 Academic Press.