PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

• Published in: Cancer cell Vol. 6; no. 4; pp. 333 - 345
• Main Authors: Cao, Renhai, Björndahl, Meit A., Religa, Piotr, Clasper, Steve, Garvin, Stina, Galter, Dagmar, Meister, Björn, Ikomi, Fumitaka, Tritsaris, Katerina, Dissing, Steen, Ohhashi, Toshio, Jackson, David G., Cao, Yihai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2004
• Subjects: Animals; Cell Division - drug effects; Cell Line; Chemotaxis - drug effects; Female; Humans; Lymphangiogenesis - drug effects; Lymphatic Metastasis; Lymphatic System - drug effects; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Neoplasms - pathology; Organ Size - drug effects; Platelet-Derived Growth Factor - pharmacology; Proto-Oncogene Proteins c-sis; Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors; Receptors, Platelet-Derived Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor - genetics; Signal Transduction - drug effects; Vascular Endothelial Growth Factor A - pharmacology
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2004.08.034

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.