Froehlich Elke V, Rinner Beate, Deutsch Alexander J A, Meditz Katharina, Knausz Heike, Troppan Katharina, Scheipl Susanne, Wibmer Christine, Leithner Andreas, Liegl Bernadette, Lohberger Birgit
Department of Orthopedic Surgery, Medical University of Graz, Graz, Austria.
J Orthop Res. 2015 May;33(5):771-8. doi: 10.1002/jor.22819. Epub 2015 Mar 13.
Chordomas mainly arise along the axial skeleton and are characterized by their slow but destructive growth. Prognosis and quality of life are poor because treatment options are mainly limited to surgery and radiotherapy. Survivin, a member of the apoptosis inhibitor protein family, functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types. The aim of this study was to determine the role of survivin in chordomas. Survivin expression was investigated in 50 chordoma samples and three chordoma cell lines using immunohistochemistry. The intensity of immunostaining was evaluated in regard to the development of recurrences. The immunohistochemical results were correlated with clinical parameters like gender, age, tumor size, and location and were performed in primary chordomas as well as in recurrent lesions. Furthermore, survivin knockdown experiments on chordoma cell lines were performed. YM155 decreased the growth behavior of chordoma cells dose- and time dependently. Transient knockdown of survivin led to a G2/M arrest, decreased proliferation, consistently induced an increase of polyploidy and morphological changes, and induced apoptosis. The resultant data from this study suggest that survivin plays a cell cycle-progressive role in chordomas. Hence, regulation of survivin by YM155 is a promising new target for the development of new therapeutic drugs.
脊索瘤主要起源于中轴骨骼，其特点是生长缓慢但具有破坏性。由于治疗选择主要限于手术和放疗，因此预后和生活质量较差。生存素是凋亡抑制蛋白家族的成员之一，作为有丝分裂和程序性细胞死亡的关键调节因子，在许多肿瘤类型中均有过表达。本研究的目的是确定生存素在脊索瘤中的作用。采用免疫组织化学方法对50例脊索瘤样本和3种脊索瘤细胞系中的生存素表达进行研究。根据复发情况评估免疫染色强度。免疫组织化学结果与性别、年龄、肿瘤大小和位置等临床参数相关，并在原发性脊索瘤和复发病变中进行。此外,还对脊索瘤细胞系进行了生存素敲低实验。YM155剂量和时间依赖性地降低了脊索瘤细胞的生长行为。生存素的瞬时敲低导致G2/M期阻滞，增殖减少，持续诱导多倍体增加和形态学改变，并诱导凋亡。本研究的结果表明生存素在脊索瘤中发挥细胞周期促进作用。因此，YM155对生存素的调节是开发新治疗药物的一个有前景的新靶点。
