Teveroni Emanuela, Di Nicuolo Fiorella, Bianchetti Giada, Epstein Alan L, Grande Giuseppe, Maulucci Giuseppe, De Spirito Marco, Pontecorvi Alfredo, Milardi Domenico, Mancini Francesca
International Scientific Institute "Paul VI", ISI, Fondazione Policlinico 'A. Gemelli' IRCCS, 00100 Rome, Italy.
Department of Neuroscience, Section of Biophysics, Università Cattolica del Sacro Cuore, 00100 Roma, Italy.
Cancers (Basel). 2021 Jan 8;13(2):212. doi: 10.3390/cancers13020212.
(1) Background: PTTG1 sustains the invasiveness of several cancer types. We previously reported that in seminomas, PTTG1 was detected in the peripheral area of the tumor and in the leading infiltrative edge. Here, we investigate the PTTG1 role on the invasive properties of seminoma. (2) Methods: three seminoma cell lines were used as in vitro model. PTTG1 levels and localization were investigated by biochemical and immunofluorescence analyses. Wound-healing, Matrigel invasion assays, and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference and overexpression experiments were performed to address the PTTG1 role in seminoma invasiveness. PTTG1 and its target MMP-2 were analyzed in human testicular tumors using the Atlas database. (3) Results: PTTG1 was highly and differentially expressed in the seminoma cell lines. Nuclear PTTG1 was positively correlated to the aggressive phenotype. Its modulation confirms these results. Atlas database analysis revealed that PTTG1 was localized in the nucleus in seminoma compared with non-seminoma tumors, and that MMP-2 levels were significantly higher in seminomas. (4) Conclusions: nuclear PTTG1 promotes invasiveness of seminoma cell lines. Atlas database supported these results. These data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.
(1) 背景:垂体瘤转化基因1(PTTG1)维持多种癌症类型的侵袭性。我们之前报道,在精原细胞瘤中,PTTG1在肿瘤周边区域和前沿浸润边缘被检测到。在此,我们研究PTTG1在精原细胞瘤侵袭特性中的作用。(2) 方法:使用三种精原细胞瘤细胞系作为体外模型。通过生化和免疫荧光分析研究PTTG1水平及定位。应用伤口愈合实验、基质胶侵袭实验和酶谱分析来研究细胞系的迁移和侵袭能力。进行RNA干扰和过表达实验以探讨PTTG1在精原细胞瘤侵袭中的作用。利用阿特拉斯数据库分析人睾丸肿瘤中的PTTG1及其靶标基质金属蛋白酶-2(MMP-2)。(3) 结果:PTTG1在精原细胞瘤细胞系中高表达且表达存在差异。细胞核内的PTTG1与侵袭性表型呈正相关。对其进行调控证实了这些结果。阿特拉斯数据库分析显示,与非精原细胞瘤肿瘤相比,PTTG1在精原细胞瘤中定位于细胞核,且精原细胞瘤中MMP-2水平显著更高。(4) 结论:细胞核内的PTTG1促进精原细胞瘤细胞系的侵袭。阿特拉斯数据库支持这些结果。这些数据提出了细胞核内PTTG1是精原细胞瘤中一个合适的预后因素的假说。