EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR DOES NOT PROMOTE TRANSFORMATION BUT CONFERS A GROWTH ADVANTAGE INVIVO TO CHINESE-HAMSTER OVARY CELLS
EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR DOES NOT PROMOTE TRANSFORMATION BUT CONFERS A GROWTH ADVANTAGE INVIVO TO CHINESE-HAMSTER OVARY CELLS
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DOI：
10.1172/jci116166
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发表时间：
1993-01-01
影响因子：
15.9
通讯作者：
LEVINSON, AD
中科院分区：
文献类型：
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作者：
FERRARA, N;WINER, J;LEVINSON, AD
血管内皮生长因子（VEGF）是一种在体外对内皮细胞具有特异性的有丝分裂原，在体内是一种血管生成诱导剂。我们测试了VEGF可能赋予表达细胞体内生长优势的假设。二氢叶酸还原酶-中国仓鼠卵巢细胞转染表达载体，指导组成型合成的VEGF。无论是表达，也不外源性管理VEGF刺激锚定依赖或锚定非依赖性生长的中国仓鼠卵巢细胞在体外。然而，与对照细胞不同，VEGF表达克隆表现出在裸鼠中增殖的能力。组织学检查显示增生性病变致密，血管化良好，无水肿。超微结构分析显示，病变内毛细血管为连续型。这些发现表明，VEGF的表达可能赋予细胞在没有转化的情况下通过纯粹的旁分泌机制在体内生长的能力。由于VEGF是一种广泛分布的蛋白质，这种性质可能与各种生理和病理增殖过程有关。
Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase- Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.