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
Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden.
Cancer Cell. 2004 Oct;6(4):333-45. 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.
癌症转移常见于淋巴系统。与肿瘤血管生成一样,肿瘤淋巴管生成的刺激可能需要多种肿瘤衍生生长因子的相互作用。在此我们报告血小板衍生生长因子(PDGF)家族成员可作为淋巴管生成因子。在体外,PDGF-BB刺激分离的淋巴管内皮细胞的丝裂原活化蛋白激酶(MAP)激酶活性和细胞运动。在体内,PDGF-BB有力地诱导淋巴管生长。PDGF-BB在小鼠纤维肉瘤细胞中的表达诱导肿瘤淋巴管生成,导致淋巴结转移增强。这些数据表明PDGF-BB是促成淋巴转移的重要生长因子。因此,阻断PDGF诱导的淋巴管生成可能为预防和治疗淋巴转移提供一种新方法。