Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine
Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine
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DOI：
10.1158/0008-5472.can-05-0623
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发表时间：
2005-12-01
期刊：
影响因子：
11.2
通讯作者：
Fidler, IJ
中科院分区：
文献类型：
--
作者：
Nilsson, MB;Langley, RR;Fidler, IJ
血管生成是恶性肿瘤生长和扩散的关键限速步骤，受正负效应之间的平衡调节。最近的研究表明，多效性细胞因子白介素6(IL-6)可能通过破坏正负向血管生成调节分子之间的平衡而参与某些肿瘤的血管形成。我们确定了IL-6是否参与了卵巢癌进展过程中观察到的血管生成。我们在体外和体内检测了人卵巢癌细胞系IL-6的产生。并不是所有的细胞株在体外都能分泌IL-6；然而，当这些细胞株被移植到雌性裸鼠的腹膜腔中时，每株细胞都能分泌IL-6。大多数受测的人卵巢癌细胞株都能分泌大量的可溶性IL-6受体(sIL-6R)。从雌性H-2K(B)-tsA58小鼠的卵巢和肠系膜建立内皮细胞系，检测其对IL-6的反应。两种内皮细胞株均表达IL-6R，外源性配体刺激可显著促进细胞迁移，激活下游信号分子信号转导和转录激活子3。IL-6R和CD31双重免疫组织化学染色显示，正常卵巢和卵巢癌标本内皮细胞表达IL-6R。将含有0.4%琼脂糖和IL-6或碱性成纤维细胞生长因子的明胶海绵植入BALB/c小鼠皮下，进行同样程度的血管化。总而言之，这些数据表明卵巢肿瘤细胞分泌IL-6，这是一种支持疾病进展的高度血管生成细胞因子。(癌症研究2005年；65(23)：10794-800)。
Angiogenesis, a key rate-limiting step in the growth and dissemination of malignant tumors, is regulated by the balance between positive and negative effectors. Recent studies indicate that the pleiotropic cytokine interleukin-6 (IL-6) may contribute to the vascularization of some tumors by disrupting the equilibrium between positive and negative angiogenic regulatory molecules. We determined whether IL-6 participates in the angiogenesis observed during the progression of ovarian carcinoma. We measured IL-6 production by human ovarian cancer cell lines in vitro and in vivo. Not all cell lines secreted IL-6 in vitro; however, when the cell lines were implanted into the peritonea] cavity of female nude mice, every line secreted IL-6. Most human ovarian carcinoma cell lines tested secreted significant levels of the soluble IL-6 receptor (slL-6R). Endothelial cell lines established from the ovary and mesentery of female H-2K(b)-tsA58 mice were tested for response to IL-6. Both endothelial cell lines expressed the IL-6R and their stimulation with the exogenous ligand significantly enhanced cell migration and activated the downstream signaling molecule signal transducers and activators of transcription 3. Dual inummohistochemical staining for IL-6R and CD31 revealed IL-6R expression on human endothelial cells within normal ovary and carcinoma specimens. Gelfoam sponges containing 0.4% agarose and IL-6 or basic fibroblast growth factor and implanted into the subcutis of BALB/c mice were vascularized to the same extent. Collectively, the data indicate that ovarian tumor cells secreted IL-6, a highly angiogenic cytokine that supports progression of disease. (Cancer Res 2005; 65(23): 10794-800).