Gastrointestinal cancer metastasis and lymphatic advancement

The role of angiogenesis in the growth of solid tumors is well established, but the role of lymphatic vessels and the relationship between lymphangiogenesis and tumor spread are less clear. Recently, the molecular pathway that signals lymphangiogenesis and specific markers for lymphatic endothelium have been discovered; however, the lymphatic pathway of cancer metastasis is only partly clarified. Several investigators from the mid 20th century indicated the existence of lymphatico-venous communications, and some observed the retrograde filling of lymph flow and lymphatico-venous communication in obstructive lymphopathy. In the 1960s Burn reported the importance of lymphovenous communication in his clinical and animal experimental data. Thus, the role of potential peripheral lymphatico-venous communication must be considered in the mechanism of cancer metastasis. We observed the lymphatico-venous (portal) communication, as well as lymph retention and reflux, in a rat model of mesenteric lymph vessel obstruction. Based on the phenomenon of lymphatico-venous communication and lymph flow reflux by lymphatic obstruction, we speculate that tumor cell obstruction in the lymph system will lead to the establishment of liver and/or peritoneal metastasis. Clinically, we observed extranodal cancer invasion in a model of lymphatic obstruction, and noted a strong relationship between extranodal invasion and liver or peritoneal metastasis. Thus, the existence of peritoneal and liver metastasis via a lymphatic pathway should be considered.