INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR-INDUCED ANGIOGENESIS SUPPRESSES TUMOR-GROWTH INVIVO
INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR-INDUCED ANGIOGENESIS SUPPRESSES TUMOR-GROWTH INVIVO
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DOI：
10.1038/362841a0
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发表时间：
1993-04-29
期刊：
影响因子：
64.8
通讯作者：
FERRARA, N
中科院分区：
文献类型：
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作者：
KIM, KJ;LI, B;FERRARA, N
新血管的发育（血管生成）是许多生理过程所必需的，包括胚胎发生、伤口愈合和黄体形成1，2。血管新生在许多疾病的发病机制中也很重要1 -5，特别是实体瘤的快速生长和转移3 -5。有几种潜在的肿瘤血管生成介质，包括碱性和酸性成纤维细胞生长因子，肿瘤坏死因子-α和转化因子-α和-β 1，2。但目前还不清楚这些药物是否真的在体内介导血管生成和肿瘤生长。血管内皮生长因子（VEGF）是一种内皮细胞特异性的有丝分裂原和血管生成诱导剂，由多种肿瘤细胞释放，并在人体肿瘤中原位表达。为了测试VEGF是否可能是体内肿瘤血管生成因子，我们将人横纹肌肉瘤、多形性胶质母细胞瘤或平滑肌肉瘤细胞系注射到裸鼠体内。我们在这里报告，治疗与VEGF特异性的单克隆抗体抑制肿瘤的生长，但在体外肿瘤细胞的生长速度没有影响。在抗体处理的肿瘤中，血管密度降低。这些发现表明，抑制肿瘤细胞自发产生的血管生成因子的作用可以抑制体内肿瘤生长。
THE development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation1,2. Blood vessel neoformation is also important in the pathogenesis of many disorders1-5, particularly rapid growth and metastasis of solid tumours3-5. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-alpha and transforming factors-alpha and -beta1,2. But it is unclear whether any of these agents actually mediates angiogenesis and tumour growth in vivo. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenesis inducer released by a variety of tumour cells and expressed in human tumours in situ. To test whether VEGF may be a tumour angiogenesis factor in vivo, we injected human rhabdomyosarcoma, glioblastoma multiforme or leiomyosarcoma cell lines into nude mice. We report here that treatment with a monoclonal antibody specific for VEGF inhibited the growth of the tumours, but had no effect on the growth rate of the tumour cells in vitro. The density of vessels was decreased in the antibody-treated tumours. These findings demonstrate that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.