Tumor Lymphangiogenesis as a Potential Therapeutic Target

Figure 2

Biology of tumor lymphangiogenesis and metastasis. (A), (B) Stimulation of tumor neo-lymphangiogenesis and enlargement of tumor lymphatics can facilitate intravasation of cancer cells into the lymphatics. (C) The interaction between tumor cells and LECs via tumor cell receptors (e.g., Integrin α4β1) and endothelial cell adhesion molecules (e.g., VCAM-1) or via chemokine receptor ligand interaction (e.g., CCR7/CCL21) can facilitate the invasion of cancer cells into lymphatic vessels (intralymphatic cancer cells). (E) Notably, lymphangiogenesis also occurs at the tumor draining lymph node (DLN) before metastasis of cancer cells to this site, probably to generate a favourable environment for in-coming metastatic cancer cells at this site. (F) Intralymphatic cancer cells then metastasize to the tumor DLN. (D), (sG) Additionally, tumor angiogenesis also contributes to distant organ metastasis. The tumor microenvironment has a critical impact on tumor progression and metastasis. LECs, lymphatic endothelial cells; DLN, draining lymph node.