Induction of lymphatic endothelial tumours: a novel model of lymphangiogenesis.

Endothelial cells form the lining of blood and lymphatic vessels. Although the endothelium of blood vessel is being extensively studied, little is known about the characteristic and the formation of lymphatic vessels. Tumours of the endothelium are divided into haemangiomas and lymphangiomas depending on whether they originate from blood or lymphatic vessels, respectively. In mice only haemangiomas have been thus far reported. The intraperitoneal injection of incomplete Freundʹs adjuvant in mice, following a standard immunization protocols, induced the development of lymphangioma in the peritoneal cavity. Histological analysis of the tumours revealed the presence of endothelial cells surrounding empty lumina and various levels of vascular development. Endothelial morphological characteristics were identified also by electromicroscopy. Immunofluorescence analysis revealed ICAM-1/CD54 expression on the cell surface of the tumour cells. The expression of VEGF, vWF, and Tyrosine Kinase Receptors (TKRs) marker genes was investigated by RT/PCR. Tumours expressed the lymphatic specific Flt-4 receptor as well as the Flk-1 and the VEGF ligand. Autocrine tumour growth was suggested by co-expression of VEGF and Flk-1. Tumour-derived cells propagate in vitro and spontaneously differentiate forming vessel-like structures indicate the maintenance of a rather normal phenotype. This system thus represents a novel in vitro model of lymphangiogenesis. The in vivo induction of lymphangioma in mice is highly reproducible and a unique source of lymphatic endothelial cells.