Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model.
Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model.
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发表时间：
2003-11
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通讯作者：
A. Byrne;Leorah Ross;J. Holash;Mikiye Nakanishi;Limin Hu;J. Hofmann;G. Yancopoulos;R. Jaffe
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作者：
A. Byrne;Leorah Ross;J. Holash;Mikiye Nakanishi;Limin Hu;J. Hofmann;G. Yancopoulos;R. Jaffe
卵巢癌是最致命的妇科恶性肿瘤，也是女性癌症的第五大常见原因。其特征是弥漫性腹膜癌病，并经常出现大量腹腔内腹水。由于血管内皮生长因子（VEGF），也称为血管通透性因子，增加血管通透性并刺激内皮细胞生长，其在卵巢癌中的作用已在许多研究中进行了评估。然而，关于VEGF单独引起腹水形成的能力和VEGF阻断抑制播散性癌症生长的能力仍然存在问题。我们已经使用逆转录病毒技术来创建过度产生VEGF的细胞群，并报告卵巢癌细胞强制表达VEGF显著减少腹水形成的时间。事实上，即使使用腺病毒载体产生的无肿瘤的VEGF腹膜过表达也足以引起腹水积聚。我们已经发现，全身施用VEGF-Trap（一种最近描述的VEGF的高亲和力可溶性诱饵受体）可以防止腹水积聚，并且还抑制播散性癌症的生长。值得注意的是，正如在南卡罗来纳州观察到的那样。在肿瘤模型中，VEGF阻断导致播散性卵巢癌中血管的显著重塑。VEGF-Trap在减少腹水和肿瘤负荷方面的有效作用表明，它将在治疗患有卵巢癌和腹水的女性的方案中具有价值。
Ovarian cancer is the most lethal gynecological malignancy and the fifth most common cause of cancer in women. It is characterized by diffuse peritoneal carcinomatosis and often by large volumes of i.p. ascites. Because vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increases vascular permeability and stimulates endothelial cell growth, its role in ovarian cancer has been evaluated in a number of studies. However, questions remain regarding the ability of VEGF alone to cause ascites formation and the ability of VEGF blockade to inhibit the growth of disseminated cancer. We have used retroviral technology to create cell populations that overproduce VEGF and report that enforced expression of VEGF by ovarian carcinoma cells dramatically reduces the time to onset of ascites formation. In fact, even tumor-free peritoneal overexpression of VEGF, created by using adenoviral vectors, is sufficient to cause ascites to accumulate. We have found that systemic administration of the VEGF-Trap, a recently described high-affinity soluble decoy receptor for VEGF, prevents ascites accumulation and also inhibits the growth of disseminated cancer. Remarkably, much as is observed in s.c. tumor models, VEGF blockade results in dramatic remodeling of the blood vessels in disseminated ovarian carcinoma. The potent effects of the VEGF-Trap in reducing both ascites and tumor burden suggest that it will be of value in a regimen for treatment of women with ovarian cancer and ascites.