Arenberg D A, Kunkel S L, Polverini P J, Glass M, Burdick M D, Strieter R M
Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.
J Clin Invest. 1996 Jun 15;97(12):2792-802. doi: 10.1172/JCI118734.
The salient feature of solid tumor growth is the strict dependence on local angiogenesis. We have previously demonstrated that IL-8 is an angiogenic factor present in freshly isolated specimens of human non-small cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesis in SCID mice, we now report that IL-8 acts as a promoter of human NSCLC tumor growth through its angiogenic properties. Passive immunization with neutralizing antibodies to IL-8 resulted in more than 40% reduction in tumor size and was associated with a decline in tumor-associated vascular density and angiogenic activity. IL-8 did not act as an autocrine growth factor for NSCLC proliferation. The reduction in primary tumor size in response to neutralizing antibodies to IL-8 was also accompanied by a trend toward a decrease in spontaneous metastasis to the lung. These data support the notion that IL-8 plays a significant role in mediating angiogenic activity during tumorigenesis of human NSCLC, thereby offering a potential target for immunotherapy against solid tumors.
实体瘤生长的显著特征是对局部血管生成的严格依赖。我们之前已经证明，白细胞介素-8（IL-8）是一种存在于新鲜分离的人非小细胞肺癌（NSCLC）标本中的血管生成因子。利用SCID小鼠中的人NSCLC肿瘤发生模型，我们现在报告IL-8通过其血管生成特性作为人NSCLC肿瘤生长的促进因子。用抗IL-8中和抗体进行被动免疫导致肿瘤大小减少超过40%，并与肿瘤相关血管密度和血管生成活性的下降有关。IL-8并非作为NSCLC增殖的自分泌生长因子。对抗IL-8中和抗体反应时原发肿瘤大小的减小还伴随着肺自发转移减少的趋势。这些数据支持这样的观点，即IL-8在人NSCLC肿瘤发生过程中介导血管生成活性方面发挥重要作用，从而为实体瘤免疫治疗提供了一个潜在靶点。
