Role of lymphangiogenic factors in tumor metastasis.
Nearly four centuries after the discovery of lymphatic vessels, the molecular mechanisms underlying their development are beginning to be elucidated. Vascular endothelial growth factor C (VEGF-C) and VEGF-D, via signaling through VEGFR-3, appear to be essential for lymphatic vessel growth. Observations from clinicopathological studies have suggested that lymphatic vessels serve as the primary route for the metastatic spread of tumor cells to regional lymph nodes. Recent studies in animal models have provided convincing evidence that tumor lymphangiogenesis facilitates lymphatic metastasis. However, it is not clear how tumor-associated lymphangiogenesis is regulated, and little is known about how tumor cells escape from the primary tumor and gain entry into the lymphatics. This review examines some of these issues and provides a brief summary of the recent developments in this field of research.
He
Yulong
Y
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, POB 63 (Haartmaninkatu 8), 00014 Helsinki, Finland.
Karpanen
Terhi
T
Alitalo
Kari
K
D000818:Animals; D006801:Humans; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000502:physiology*; D009336:Necrosis; D009362:Neoplasm Metastasis / Q000276:immunology / Q000503:physiopathology*; D042582:Vascular Endothelial Growth Factor C / Q000502:physiology*; D042643:Vascular Endothelial Growth Factor D / Q000502:physiology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors / Q000502:physiology
D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3