COX-2 induces IL-11 production in human breast cancer cells
COX-2 induces IL-11 production in human breast cancer cells
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DOI：
10.1016/j.jss.2005.11.582
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发表时间：
2006-04-01
影响因子：
2.2
通讯作者：
Lucci, A
中科院分区：
文献类型：
--
作者：
Singh, B;Berry, JA;Lucci, A
背景环氧合酶-2（考克斯-2）在40%的人浸润性乳腺癌中过表达。白细胞介素-11（IL-11）是破骨细胞生成的有效介质，参与乳腺癌骨转移。由于过表达考克斯-2的乳腺癌与较高的骨转移率相关，我们假设肿瘤细胞中的考克斯-2表达将诱导IL-11。我们用考克斯-2表达载体转染MCF-7（低转移性）和MDA-231（高转移性）人乳腺癌细胞系。Western blot和PGE（2）免疫法检测考克斯-2的表达，免疫法检测IL-11的产生。我们还使用了裸鼠模型来研究转移到骨的乳腺癌细胞产生的考克斯-2和IL-11。从长骨软骨中分离培养趋骨克隆（BSC）。考克斯-2转染导致MCF-7和MDA-231细胞中IL-11产生增加约5- 6倍。与亲本MDA-435 S-COX 2细胞相比，MDA-435 S-COX 2-BSC（从骨转移中分离的细胞）产生升高水平的IL-11和PGE（，）（考克斯-2的重要介质）。此外，低浓度NS-398或塞来昔布可显著降低考克斯-2转染的MDA-231细胞中IL-11的产生，从而证实考克斯-2参与IL-11的诱导。乳腺癌细胞中考克斯-2介导的IL-11的产生可能对乳腺癌患者溶骨性骨转移的发展至关重要，考克斯-2抑制剂可能有助于抑制该过程。(C)2006年爱思唯尔公司保留所有权利。
Background. Cyclooxygenase-2 (COX-2) is overexpressed in 40% of human invasive breast cancers. Interleukin-11 (IL-11), a potent mediator of osteoclastogenesis, is involved in breast cancer metastasis to bone. Since breast cancers that overexpress COX-2 are associated with a higher rate of metastasis to bone, we hypothesized that COX-2 expression in tumor cells would induce IL-11.Materials and methods. We transfected MCF-7 (poorly metastatic) and MDA-231 (highly metastatic) human breast cancer cell lines with COX-2 expression vectors. COX-2 overexpression was confirmed by Western blot and PGE(2) immunoassay, and IL-11 production was measured by immunoassay. We also used a nude mouse model to study COX-2 and IL-11 production from breast cancer cells that metastasized to bone. The bone-seeking clones (BSC) were isolated and cultured from the long bone metastases.Results. COX-2 transfection caused an approximately 5- to 6-fold increase in IL-11 production in both MCF-7 and MDA-231 cells. MDA-435S-COX2-BSC (cells isolated from bone metastasis) produced elevated levels of IL-11 and PGE(,) (an important mediator of COX-2) as compared to the parental MDA-435S-COX2 cells. Furthermore, a treatment with low I- to 2-mu M concentration NS-398 or Celecoxib significantly reduced the production of IL-11 in COX-2-transfected MDA-231 cells, thus confirming the involvement of COX-2 in IL-11 induction.Conclusion. COX-2-mediated production of IL-11 in breast cancer cells may be vital to the development of osteolytic bone metastases in patients with breast cancer, and a COX-2 inhibitor may be useful in inhibiting this process. (C) 2006 Elsevier Inc. All rights rcserved.