缺氧导致的病理性血管再生与肿瘤迁移.ppt

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model Hypoxia—VEGF—Angiogenesis—Metastasis 概要 Mechanisms underlying pathological angiogenesis in relation to hypoxia in tumor invasion and metastasis remain elusive. Tumor microvascular networks possess several unique pathological features including extremely high densities of leaky, tortuous, and primitive microvessels that usually lack pericyte coverage, base-ment membrane, and arteriole-venule distinctions . Although hypoxia often results in necrosis of the central core of a fast-growing tumor, it could potentially persuade tumor cells to invade neighboring healthy vasculatures for survival, eventually leading to metastasis, which is one of the hallmarks for cancer therapy. A clinical detectable metastatic mass often represents an ultimate consequence of several distinctive steps of the metastatic cascade, including dissemination of malignant cells from the primary site, transport of tumor cells via the circulation or lymphatic system, adhesion of tumor cells in distal tissues/organs, and re-growth of tumor cells into a detectable mass. Clinical detection of a metastasis does not reveal early events of tumor cell dissemination and intimate interactions between tumor cells and microvessels. So the the cancer therapy is difficult. We have developed a zebra?sh tumor model that allows us to study the role of pathological angiogenesis under normoxia and hypoxia in arbitrating early events of the metastatic cascade at the single cell level. Hypoxia and VEGF signaling pathway significantly contribute to early events of the metastatic cascade. The ?ndings also shed light on molecular mechanisms of bene?cial effects of clinically available anti-VEGF drugs for cancer therapy. 方法和结果 1 Hypoxic Metastasis Model in Zebrafish The Tg(fli1:EGFP) zebrafish embryos Murine T241 tumor cells were labeled with DiI dye in vitro and labeled cells were inje