Oncostatin M induces cell detachment and enhances the metastatic capacity of T-47D human breast carcinoma cells
Oncostatin M induces cell detachment and enhances the metastatic capacity of T-47D human breast carcinoma cells
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DOI：
10.1016/j.cyto.2006.03.004
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发表时间：
2006-03-21
期刊：
影响因子：
3.8
通讯作者：
Ryan, Randall E.
中科院分区：
文献类型：
--
作者：
Jorcyk, Cheryl L.;Holzer, Ryan G.;Ryan, Randall E.
抑瘤素M（OSM）是一种IL-6家族细胞因子，先前已显示可增加几种乳腺癌细胞系的体外迁移。我们的研究报告了OSM处理对人乳腺癌细胞系T-47 D的额外影响。OSM处理将T-47 D细胞形态从正常上皮表型改变为与细胞从基质脱离相关的间充质样表型。H3922人乳腺癌细胞也观察到这些效应。OSM处理T-47 D细胞5-8天导致细胞脱离增加三倍。蛋白激酶抑制剂UO 126和双吲哚马来酰亚胺阻断了OSM诱导的T-47 D细胞脱离，表明MAP激酶和蛋白激酶C在调节细胞脱离的OSM信号传导事件中的作用。与其他细胞外基质组分相比，由OSM诱导分离的T-47 D细胞具有降低的重新粘附层粘连蛋白的能力。T-47 D细胞的分离的多细胞聚集体是活的，而分离的单细胞出现凋亡。此外，OSM处理诱导T-47 D细胞分泌溶酶体蛋白酶组织蛋白酶D和L，其与侵袭和转移有关。重要的是，OSM处理的T-47 D细胞显示如通过Matrigel侵袭室测定所测量的侵袭能力增加250%。总的来说，这些数据表明OSM在体外诱导T-47 D细胞的运动/侵袭表型，并表明OSM可能增强体内转移。我们的研究结果表明，OSM本身可能是一个有效的治疗靶点。(c)2006爱思唯尔有限公司保留所有权利。
Oncostatin M (OSM), an IL-6 family cytokine, has previously been shown to increase migration of several breast cancer cell lines in vitro. Our studies report additional effects of OSM treatment on the human breast carcinoma cell line T-47D. OSM treatment alters T-47D cell morphology from a normal epithelial phenotype to a mesenchymal-like phenotype that is associated with cell detachment from substratum. These effects are also seen with H3922 human breast cancer cells. OSM treatment of T-47D cells for 5-8 days leads to a three-fold increase in cell detachment. OSM-induced detachment of T-47D cells is blocked by the protein kinase inhibitors UO126 and bisindolylmaleimide, indicating a role for MAP kinases and protein kinase C in OSM signaling events that regulate cell detachment. T-47D cells induced to detach by OSM have a reduced capacity to re-adhere to laminin in comparison to other extracellular matrix components. Detached multi-cell aggregates of T-47D cells are viable, whereas detached single cells appear apoptotic. In addition, OSM treatment induces the secretion of the lysosomal proteases cathepsins D and L from T-47D cells, which have been implicated in invasion and metastasis. Importantly, OSM-treated T-47D cells show a 250% increase in invasive capacity as measured by the Matrigel invasion chamber assay. Collectively, these data demonstrate that OSM induces a motile/invasive phenotype in T-47D cells in vitro, and suggest that OSM may enhance metastasis in vivo. Our results suggest that OSM itself may be a valid therapeutic target. (c) 2006 Elsevier Ltd. All rights reserved.