FINE STRUCTURE OF THE ABSORBING LYMPHATIC VESSEL AND INTRAVASATION MODALITY OF THE CANCER CELL

The topografic distribution and the fine structure of the tumor-associated absorbing lymphatic vessel in the B16 Melanoma and T84 adenocarcinoma subcutaneous tumor mass of nude mice and in adenocarcinoma mouse prostate in transgenic mice were studied to demonstrate the modality of the cancer cell transendothelial migration and the role of the lymphatic pathway in the metastatic diffusion. Furthermore, the structural characteristics of the lymphatic vascular system canalisation, that allow to discriminate between the vessels with high absorbent capacity, distinctive of the mucous and submucous network and vessels with lymph flow and conduction function (precollectors, pre- and postlymph nodal collectors, etc.), are specified. The presence of lymphatic vessels was revealed by LYVE-1 and D2-40 markers, only at the borders of the tumor mass and in the peritumoral tissue. These vessels are characterized by a monolayer of endothelial cells joined each other by overlapping contacts and often they contract close connection with the cancer cell evolved in the invasive phenotype. The serial ultrastructural pictures of the latter and their three-dimensional model reconstructions allow to evidence the modality of their passage from the interstitial matrix into the lymphatic vessel lumen that takes place by means of intraendothelial channel formation without committing the interendothelial junctions. The intraendothelial channel is formed by the peculiar behaviour of the non nuclear cytoplasm of two adjacent endothelial cells and is the first morphological documentation of the cancer cell intravasation into lymphatic circulation and its lymph node metastatization. The molecular bases that control the constitution of the intraendothelial channel and the mechanism of the active transendothelial migration of the cancer cell are unknown, but the role of the vascular endothelial growth factor –C and D, and of the chemoattractants released from matrix and from lymphatic endothelium seems to be accepted.