Abstract
Cancer metastases are commonly found in the lymphatic system. Like tumor blood angiogenesis, stimulation of tumor lymphangiogenesis may require the interplay of several tumor-derived growth factors. Here we report that members of the PDGF family act as lymphangiogenic factors. In vitro, PDGF-BB stimulated MAP kinase activity and cell motility of isolated lymphatic endothelial cells. In vivo, PDGF-BB potently induced growth of lymphatic vessels. Expression of PDGF-BB in murine fibrosarcoma cells induced tumor lymphangiogenesis, leading to enhanced metastasis in lymph nodes. These data demonstrate that PDGF-BB is an important growth factor contributing to lymphatic metastasis. Thus, blockage of PDGF-induced lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Becaplermin
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Cell Division / drug effects
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Cell Line
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Chemotaxis / drug effects
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Female
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Humans
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Lymphangiogenesis / drug effects*
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Lymphatic Metastasis*
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Lymphatic System / drug effects
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Male
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Mice
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Mice, Inbred C57BL
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Neoplasms / pathology*
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Organ Size / drug effects
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Platelet-Derived Growth Factor / pharmacology*
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Proto-Oncogene Proteins c-sis
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Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
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Receptors, Platelet-Derived Growth Factor / metabolism
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Receptors, Vascular Endothelial Growth Factor / genetics
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Signal Transduction / drug effects
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Vascular Endothelial Growth Factor A / pharmacology
Substances
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins c-sis
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Vascular Endothelial Growth Factor A
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platelet-derived growth factor A
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platelet-derived growth factor AB
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Becaplermin
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Receptors, Platelet-Derived Growth Factor
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Receptors, Vascular Endothelial Growth Factor