Liu J, Hadjokas N, Mosley B, Estrov Z, Spence M J, Vestal R E
Department of Veterans Affairs Medical Center, Mountain States Medical Research Institute, Boise, Idaho 83702, USA.
Cytokine. 1998 Apr;10(4):295-302. doi: 10.1006/cyto.1997.0283.
Oncostatin M (OSM) is a cytokine produced by activated T lymphocytes and macrophages. OSM is structurally and functionally related to leukaemia inhibitory factor (LIF), another cytokine in the interleukin 6 (IL-6) family. The biological activities of OSM are mediated through two types of receptor complexes, the LIF/OSM shared receptor (type I) and OSM-specific receptor (OSM-R, type II), which is composed of gp130 as a binding subunit and a newly identified affinity conversion subunit, OSM-R beta. Previous research conducted in the authors' laboratory has shown that OSM inhibits the growth of several breast cancer cell lines. To investigate whether OSM has a similar effect in primary normal human mammary epithelial (HME) cells, the activity of OSM in HME cells derived from four donors was examined. OSM produced a dose-dependent inhibition of DNA synethesis in these cells. In order to determine the receptor subtypes mediating OSM activity in HME and breast cancer cells, flow cytometry analysis using anti-gp130mAb and anti-OSM-R beta mAb was performed. In these studies, the authors were able to examine expressions of gp130 and OSM-R beta. In addition, quantitative RT-PCR assays were conducted to measure expressions of the mRNAs of the subunits for type I and type II OSM receptor. The results show that HME cells and most breast cancer cell lines express both the type I and the type II OSM receptors. However, type II, OSM-specific receptors are expressed at a higher levels than type I, OSM/LIF shared receptors. Accordingly, we compared the growth regulatory activities of OSM with LIF in HME cells and in breast cancer cells. In contrast to the inhibitory activity of OSM, LIF stimulated the growth of breast cancer cells, whereas it had no effect on normal mammary epithelial cell growth. Together, these data suggest that OSM plays an inhibitory role in normal and malignant mammary epithelial cell growth in vitro. OSM activity is mediated by the OSM-specific receptor (type II), not by the OSM/LIF shared receptor.
抑瘤素M（OSM）是一种由活化的T淋巴细胞和巨噬细胞产生的细胞因子。OSM在结构和功能上与白血病抑制因子（LIF）相关，LIF是白细胞介素6（IL-6）家族中的另一种细胞因子。OSM的生物学活性通过两种类型的受体复合物介导，即LIF/OSM共享受体（I型）和OSM特异性受体（OSM-R，II型），后者由gp130作为结合亚基和新鉴定的亲和力转换亚基OSM-Rβ组成。作者实验室之前的研究表明，OSM可抑制多种乳腺癌细胞系的生长。为了研究OSM在原代正常人乳腺上皮（HME）细胞中是否具有类似作用，检测了来自四名供体的HME细胞中OSM的活性。OSM对这些细胞的DNA合成产生了剂量依赖性抑制。为了确定介导OSM在HME细胞和乳腺癌细胞中活性的受体亚型，使用抗gp130单克隆抗体和抗OSM-Rβ单克隆抗体进行了流式细胞术分析。在这些研究中，作者能够检测gp130和OSM-Rβ的表达。此外，进行了定量逆转录-聚合酶链反应（RT-PCR）分析以测量I型和II型OSM受体亚基的mRNA表达。结果表明，HME细胞和大多数乳腺癌细胞系均表达I型和II型OSM受体。然而，II型OSM特异性受体的表达水平高于I型OSM/LIF共享受体。因此，作者比较了OSM和LIF在HME细胞和乳腺癌细胞中的生长调节活性。与OSM的抑制活性相反，LIF刺激乳腺癌细胞的生长，而对正常乳腺上皮细胞的生长没有影响。总之，这些数据表明OSM在体外对正常和恶性乳腺上皮细胞生长起抑制作用。OSM的活性由OSM特异性受体（II型）介导，而非由OSM/LIF共享受体介导。
