Smith D R, Polverini P J, Kunkel S L, Orringer M B, Whyte R I, Burdick M D, Wilke C A, Strieter R M
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0360.
J Exp Med. 1994 May 1;179(5):1409-15. doi: 10.1084/jem.179.5.1409.
We investigated the role of interleukin 8 (IL-8) in mediating angiogenesis in human bronchogenic carcinoma. Increased quantities of IL-8 were detected in tumor tissue as compared with normal lung tissue. Immunohistochemical staining of tumors revealed primary localization of IL-8 to individual tumor cells and demonstrated the capacity of tumor to elaborate IL-8. Functional studies that used tissue homogenates of tumors demonstrated the induction of both in vitro endothelial cell chemotaxis and in vivo corneal neovascularization. It is important to note that the addition of neutralizing antisera to IL-8 to these assays resulted in the marked and specific attenuation of these responses. Our observations definitively establish IL-8 as a primary mediator of angiogenesis in bronchogenic carcinoma and offer a potential target for immunotherapies against solid malignancies.
我们研究了白细胞介素8(IL-8)在介导人类支气管源性癌血管生成中的作用。与正常肺组织相比,在肿瘤组织中检测到IL-8的量增加。肿瘤的免疫组织化学染色显示IL-8主要定位于单个肿瘤细胞,并证明肿瘤具有分泌IL-8的能力。使用肿瘤组织匀浆进行的功能研究表明,体外可诱导内皮细胞趋化性,体内可诱导角膜新生血管形成。需要注意的是,在这些试验中加入针对IL-8的中和抗血清会导致这些反应显著且特异性减弱。我们的观察结果明确证实IL-8是支气管源性癌血管生成的主要介质,并为针对实体恶性肿瘤的免疫疗法提供了一个潜在靶点。