Interleukin-12 inhibits tumor growth in a novel angiogenesis canine hemangiosarcoma xenograft model
Interleukin-12 inhibits tumor growth in a novel angiogenesis canine hemangiosarcoma xenograft model
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DOI：
10.1593/neo.03334
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发表时间：
2004-03-01
期刊：
影响因子：
4.8
通讯作者：
Helfand, SC
中科院分区：
文献类型：
--
作者：
Akhtar, N;Padilla, ML;Helfand, SC
我们建立了一个犬血管肉瘤细胞系衍生自恶性内皮细胞，包括一个自发性肿瘤的狗，提供一个可再生的内皮细胞来源的研究血管生成的恶性肿瘤。将血管肉瘤活检组织块皮下移植到bg/nu/XID小鼠中，使肿瘤细胞在体内扩增。细胞系SB-HSA来源于异种移植物。SB-HSA细胞表达血管内皮生长因子（VEGF）受体1和2、CD 31、CD 146和α v β 3整联蛋白，并产生几种生长因子和细胞因子，包括VEGF、碱性成纤维细胞生长因子和刺激内皮细胞生长的白细胞介素（IL）-8。这些结果表明，该细胞再现了有丝分裂激活的内皮细胞的特征。在体内，SB-HSA细胞在小鼠中刺激了强烈的血管生成反应，并在免疫功能低下的小鼠中形成了由异常血管通道组成的肿瘤块，为研究抗血管生成剂的有效性提供了新的机会。使用该模型，我们确定了IL-12，一种具有免疫刺激和抗血管生成作用的细胞因子，抑制了SB-HSA细胞诱导的血管生成和肿瘤生长。我们所描述的内皮细胞模型提供了独特的机会，进一步研究IL-12，以及其他抗血管生成的方法在癌症治疗。
We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF) receptors 1 and 2, CD31, CD146, and alphavbeta3 integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL)-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.