Medical Research Center for Ischemic Tissue Regeneration & Medical Research Institute, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Int J Biochem Cell Biol. 2013 Aug;45(8):1869-77. doi: 10.1016/j.biocel.2013.05.027. Epub 2013 Jun 2.
Oncostatin M, a member of the interleukin-6 family of cytokines, has been implicated in tumorigenesis of human prostate cancer. In the current study, we demonstrate that oncostatin M promotes human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth in an in vivo xenograft transplantation model of the human prostate cancer cell line PC-3M-luc-C6, a PC3M cell line expressing the luciferase gene. Conditioned medium derived from oncostatin M-treated mesenchymal stem cells stimulated adhesion of PC-3M-luc-C6 cells. We identified TGFBI and periostin, extracellular matrix proteins implicated in tumorigenesis and metastasis, as oncostatin M-induced secreted proteins in mesenchymal stem cells. Treatment with oncostatin M stimulated secretion of periostin and TGFBI from mesenchymal stem cells in a time-dependent manner. Immunodepletion of TGFBI and periostin from conditioned medium derived from oncostatin M-treated mesenchymal stem cells resulted in abrogation of adhesion of PC-3M-luc-C6 cells stimulated by oncostatin M-conditioned medium. In addition, small interfering RNA-mediated silencing of TGFBI and periostin resulted in abrogation of cell adhesion stimulated by oncostatin M-conditioned medium. These results suggest that mesenchymal stem cell-derived TGFBI and periostin play a key role in tumorigenesis by stimulating adhesion of prostate cancer cells.
抑瘤素 M 是白细胞介素-6 家族细胞因子的成员，已被牵涉到人类前列腺癌的肿瘤发生中。在本研究中，我们证明了抑瘤素 M 通过人前列腺癌细胞系 PC-3M-luc-C6 的体内异种移植移植模型促进了人脂肪组织来源的间充质干细胞刺激的肿瘤生长，该细胞系表达荧光素酶基因。来自抑瘤素 M 处理的间充质干细胞的条件培养基刺激了 PC-3M-luc-C6 细胞的黏附。我们鉴定了 TGFBI 和 periostin，这两种细胞外基质蛋白与肿瘤发生和转移有关，是间充质干细胞中抑瘤素 M 诱导的分泌蛋白。抑瘤素 M 以时间依赖性方式刺激间充质干细胞中 periostin 和 TGFBI 的分泌。用免疫沉淀法从抑瘤素 M 处理的间充质干细胞的条件培养基中去除 TGFBI 和 periostin，可消除由抑瘤素 M 条件培养基刺激的 PC-3M-luc-C6 细胞的黏附。此外，通过小干扰 RNA 介导的 TGFBI 和 periostin 沉默，可消除由抑瘤素 M 条件培养基刺激的细胞黏附。这些结果表明，间充质干细胞衍生的 TGFBI 和 periostin 通过刺激前列腺癌细胞的黏附在肿瘤发生中发挥关键作用。
