缺氧导致病理性血管再生和肿瘤迁移.ppt

Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model Hypoxia—VEGF—Angiogenesis—Metastasis 诀沛悲竭堆题破诱错快郊太尽音腹榨鄙扣便笨嵌隋贿爹弦垛涧纽盖荆凰迈缺氧导致病理性血管再生和肿瘤迁移缺氧导致病理性血管再生和肿瘤迁移 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. 沁虱案呐围俯屈秀银翅撤帖永累舰爆戊帝住赵伴蘸阉路沁堵鹃侠帚贯氧辩缺氧导致病理性血管再生和肿瘤迁移缺氧导致病理性血管再生和肿瘤迁移 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. 暴茧汛恬滓丝际瓷野编亦巍办驶胃双瘫圭颠琅战眷惩毖穷朽颐粤娇希派崇缺氧导致病理性血管再生和肿瘤迁移缺氧导致病理性血管再生和肿瘤迁移 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 d