Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor.
Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor.
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发表时间：
1991-11
期刊：
影响因子：
11.2
通讯作者：
A. Hori;R. Sasada;E. Matsutani;K. Naito;Y. Sakura;T. Fujita;Y. Kozai
中科院分区：
文献类型：
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作者：
A. Hori;R. Sasada;E. Matsutani;K. Naito;Y. Sakura;T. Fujita;Y. Kozai
碱性成纤维细胞生长因子(碱性成纤维细胞生长因子)是一种强有力的血管生成有丝分裂原。为阐明碱性成纤维细胞生长因子抑制剂在体内的作用，制备了抗碱性成纤维细胞生长因子免疫中和单抗。通过细胞融合获得的抗人bFGF的单抗3H3在100 ng/ml的浓度下可完全抑制bFGF诱导的人脐静脉内皮细胞的增殖，3H3不与酸性成纤维细胞生长因子或HST1蛋白结合，表明其具有很高的特异性。此外，还检测了3H3的体内免疫中和活性。K1000细胞(BALB/c 3T3转化子，在其中导入了前导序列融合的bFGF基因)被移植到sc。移植到BALB/c裸鼠体内。静脉注射可抑制肿瘤细胞的生长。浓度为200微克/只的3H3处理。组织学观察表明，3H3的抗肿瘤作用是通过抑制bFGF诱导的血管生成而实现的。本实验为肿瘤生长依赖血管生成的假说提供了直接的因果证据。这一发现也可能对血管生成实体瘤的新治疗方法的开发有意义。
Basic fibroblast growth factor (bFGF) is a potent angiogenic mitogen. To elucidate the effect of bFGF inhibitors in vivo, anti-bFGF immunoneutralizing monoclonal antibody was prepared. One monoclonal antibody against human bFGF, obtained by cell fusion and designated 3H3, completely inhibited bFGF-induced proliferation of human umbilical vein endothelial cells at a concentration of 100 ng/ml. 3H3 did not bind to acidic fibroblast growth factor or HST1 protein, indicating high specificity for bFGF. Furthermore, the immunoneutralizing activity of 3H3 was examined in vivo. K1000 cells (a BALB/c 3T3 transformant in which the leader sequence-fused bFGF gene was transfected) were transplanted s.c. into BALB/c nude mice. Growth of the tumor cells was inhibited by i.v. treatment with 3H3 at a concentration of 200 micrograms/mouse. Histological observation showed that the antitumor effect of 3H3 was due to the inhibition of bFGF-induced angiogenesis. This experiment provides direct causal evidence for the hypothesis that tumor growth is angiogenesis dependent. This finding could also have implications for the development of novel therapeutic approaches to angiogenic solid tumors.