Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment.
Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment.
复制标题
通过中和抗体靶向骨源性胰岛素样生长因子-II，可抑制人骨环境中前列腺癌细胞的生长。
DOI：
10.1158/1078-0432.ccr-09-0982
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Ochiai A
中科院分区：
文献类型：
--
作者：
Kimura T;Kuwata T;Ashimine S;Yamazaki M;Yamauchi C;Nagai K;Ikehara A;Feng Y;Dimitrov DS;Saito S;Ochiai A
晚期前列腺癌经常累及骨骼，骨骼中富含胰岛素样生长因子 (IGF)-2。然而，IGF-2 在前列腺癌骨转移中的重要性尚不确定。本研究旨在探讨靶向 IGF-2 在前列腺癌骨转移中的治疗重要性。我们研究了使用人中和抗体 (m610) 抑制 IGF-2 是否会抑制人骨环境中前列腺癌细胞的生长。将人MDA PCa 2b前列腺癌细胞接种到植入非肥胖糖尿病/严重联合免疫缺陷小鼠乳腺脂肪垫的成人骨中，或接种到未植入人骨的小鼠乳腺脂肪垫中。在接种 MDA PCa 2b 细胞后，立即用 m610 或对照抗体 (m102.4) 每周一次处理小鼠，持续 4 周。组织形态学检查表明，与对照相比，m610处理显着减少了人骨中的MDA PCa 2b肿瘤面积。 Ki-67免疫染色显示，m610处理的骨肿瘤切片中增殖癌细胞的百分比显着低于对照。在没有植入人骨的情况下，M610 对 MDA PCa 2b 肿瘤生长没有影响。 M610 阻止体外 IGF-2 诱导的 MDA PCa 2b 细胞增殖。我们的研究结果表明，IGF-2 在人骨中前列腺癌细胞的生长中发挥着重要作用，这表明通过中和抗体靶向 IGF-2 为前列腺癌骨转移提供了一种新的治疗策略。
Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-2 is abundant. However, the importance of IGF-2 in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-2 in bone metastases from prostate cancer. We investigated whether inhibiting IGF-2 using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of non-obese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells. Histomorphological examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. M610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. M610 prevented the in vitro IGF-2-induced proliferation of MDA PCa 2b cells. Our results indicate that IGF-2 plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer.