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      PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.

      Cancer Cell
      Animals, Cell Division, drug effects, Cell Line, Chemotaxis, Female, Humans, Lymphangiogenesis, Lymphatic Metastasis, Lymphatic System, Male, Mice, Mice, Inbred C57BL, Neoplasms, pathology, Organ Size, Platelet-Derived Growth Factor, pharmacology, Proto-Oncogene Proteins c-sis, Receptors, Platelet-Derived Growth Factor, antagonists & inhibitors, metabolism, Receptors, Vascular Endothelial Growth Factor, genetics, Signal Transduction, Vascular Endothelial Growth Factor A

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          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.

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