Prospects for Vasculature Reorganization in Sentinel Lymph Nodes

Primary tumors can induce vasculature and lymph channel reorganizations within sentinel lymph nodes before the arrival of cancer cells. The key blood vessels in such nodes that are remodeled are high endothelial venules (HEVs). The morphological alteration of HEVs in the presence of a cancer, coupled with the increased proliferation rate of the endothelial cells, results in a functional shifting of HEVs from immune response to blood-flow carrier. This tumor-induced reorganization is quite different from an endotoxin-induced inflammatory vasculature alteration. We review some of the accepted doctrines on lymph flow and lymphatic metastasis in light of this reorganization. More investigations are needed to elucidate the molecular mechanisms underlying the morphological and functional alteration of HEVs, the fluid exchanges between lymph and blood, the microenvironmental preparation for cancer cells to survive and expand in the lymph node, and the detail process of further distant dissemination of cancer cells from the lymph nodes. Further study of this pathological process may help to explain some clinical phenomena, and should aid in developing novel therapeutics and prevention strategies against cancer metastasis.