[Lymphodynamic factors governing lymphatic spread of carcinoma cells].
Carcinoma frequently spreads and grows through the lymphatic system, whereas malignant tumors of mesenchymal origin more frequently spread via the hematogenous route. This paper reviews cancer spread with special reference to tumor microcirculation, vascular endothelial growth factor receptor (VEGFR)-3-mediated lymphangiogenesis, regeneration of collecting lymph vessels, and the role of nitric oxide in lymphatic metastasis. Oxygen and pH are key microenvironmental factors in the development and growth of tumors and their response to treatment. Thus the physiological and pathophysiological roles of hypoxia and acidic pH in the tumor microenvironment in lymphatic metastasis are demonstrated. Lymph angiogenesis in tumor tissues and regeneration of collecting lymph vessels with special reference to VEGFR-3 and its agonists VEGF-C/VEGF-D are discussed. The occurrence and biological significance of intratumoral lymph angiogenesis in breast cancer have been established. VEGF-C as a molecular link between tumor lymph angiogenesis and metastasis is identified. Finally, the role of nitric oxide (NO) in tumor microcirculation and lymphatic metastasis of carcinoma cells is evaluated.
Ohhashi
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First Department of Physiology, Shinshu University School of Medicine, Japan.
D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008208:Lymphatic System / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D040321:Vascular Endothelial Growth Factor Receptor-3
D017978:Receptors, Growth Factor; D009569:Nitric Oxide; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3