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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.

Original publication

DOI

10.1016/j.ccr.2004.08.034

Type

Journal article

Journal

Cancer Cell

Publication Date

10/2004

Volume

6

Pages

333 - 345

Keywords

Animals, Cell Division, Cell Line, Chemotaxis, Female, Humans, Lymphangiogenesis, Lymphatic Metastasis, Lymphatic System, Male, Mice, Mice, Inbred C57BL, Neoplasms, Organ Size, Platelet-Derived Growth Factor, Proto-Oncogene Proteins c-sis, Receptors, Platelet-Derived Growth Factor, Receptors, Vascular Endothelial Growth Factor, Signal Transduction, Vascular Endothelial Growth Factor A