Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells

Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells
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DOI:
10.1016/s0304-3835(99)00401-2
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发表时间:
2000-04-03
期刊:
影响因子:
9.7
通讯作者:
Lahm, H
Lahm, H
中科院分区:
医学1区
文献类型:
--
作者:
Schneider, MR;Hoeflich, A;Lahm, H

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白介素6(IL-6)是一种多效性细胞因子,对包括肿瘤细胞在内的多种细胞具有生物活性。我们研究了IL-6对人结直肠癌细胞株的生物学作用及IL-6受体(IL-6R)的表达。Isreco-1来源于结肠癌原发灶,而Isreco-2和Isreco-3来源于同一患者的肝和腹膜转移,IL-6刺激Isreco-1细胞甲基纤维素集落形成率达150%(P<0.05)。这种影响在转移的Isreco-2细胞系上更加明显,在IL-6存在的情况下,集落数量以剂量依赖的方式增加到四倍(P<0.0001)。抗IL-6抗体完全阻断了IL-6的这种促生长作用,RT-PCR分析显示IL-6Rα和gp130在这些细胞系中有转录,额外的细胞株实验证实了gp130的普遍表达,但显示IL-6Rα链的有限表达。令人惊讶的是,在测试的细胞系中,约有一半的细胞低水平表达IL-6mRNA,而IL-6mRNA不能转化为蛋白质。我们的结果表明,IL-6可以有效地刺激某些结直肠癌细胞的贴壁非贴壁生长。这种刺激似乎是通过旁分泌机制发生的。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
Interleukin-6 (IL-6) is a pleiotropic cytokine which exerts biological activities on various cell types including neoplastic cells. We have investigated the biological effect of IL-6 and the expression of IL-6 receptors (IL-6R) on human colorectal carcinoma cell lines. Isreco-1 was derived from the primary site of a colon cancer while Isreco-2 and Isreco-3 were established from a liver and peritoneal metastasis of the same patient, IL-6 stimulated colony formation in methylcellulose of Isreco-1 cells to 150% (P < 0.05). The effect was even more pronounced on the metastatic Isreco-2 line where colony numbers in the presence of IL-6 were enhanced up to four-fold (P < 0.0001) in a dose-dependent fashion. An anti-IL-6 antibody completely abolished this growth stimulatory effect of IL-6, RT-PCR analysis revealed transcripts for IL-6R alpha and gp130 in these cell lines, Experiments with additional cell lines confirmed the general expression of gp130 but showed limited expression of the IL-6R alpha chain. Surprisingly, about half of the cell lines tested expressed IL-6 mRNA at low levels which was not translated into protein. Our results suggest that IL-6 can potently stimulate anchorage-independent growth of some colorectal carcinoma cells. This stimulation appears to occur through a paracrine mechanism. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.