Grande Giuseppe, Milardi Domenico, Martini Maurizio, Cenci Tonia, Gulino Gaetano, Mancini Francesca, Bianchi Antonio, Pontecorvi Alfredo, Pierconti Francesco
Division of Endocrinology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
International Scientific Institute Paul VI, Rome, Italy.
Front Endocrinol (Lausanne). 2019 Sep 11;10:619. doi: 10.3389/fendo.2019.00619. eCollection 2019.
Seminomas are the most frequent kind of testicular germ cell tumors (TGCTs), accounting for 50% of tumor diagnosis in young men, whereas non-seminomas account for 40% and mixed forms for 10% of cases. It is currently supposed that TGCTs evolve from a pre-invasive stage of carcinoma (CIS). Octamer-binding transcription factor 4 (OCT4) is essential for self-renewal of stem cells. It is considered as a major regulator of cell pluripotency. Prior studies have shown that seminoma expresses OCT4. Transcription factor Krüppel-like factor 4 (KLF4) has moreover associated with embryonic stem cell maintenance. Finally, we previously demonstrated the expression of PTTG1 in CIS and seminomas. In this pilot study, we compared the combined expression of PTTG1 with KLF4 and OCT4 in seminoma, in order to validate our hypotesis that PTTG1 marks a specific population of stem cells in neoplastic tissue, strictly related with tumor. Formalin-fixed and paraffin-embedded testicular tissues by 5 patients who underwent an orchidectomy for seminoma have been collected and immunofluorescence analysis was performed using antibody rabbit monoclonal PTTG-1 and mouse monoclonal OCT4 or mouse monoclonal KLF4 antibody. In seminoma we observed that tumor cells strongly express OCT-4 in all seminomas and in the intratubular areas of seminoma. Expression of KLF-4 was observed in many tumor cells. PTTG1 marks some specific OCT4- and KLF4-positive tumor cells, mainly localized at the periphery of the neoplasm. In the intertubular infiltration areas nests of cells expressing both OCT4/KLF4 and PTTG1 have been observed. This is the first identification of a cell population in seminoma characterized for being OCT4, KLF4, and PTTG1 positive cells in seminoma, associated with cancer invasiveness. Further investigation is needed to elucidate if a functional abrogation of PTTG1 might be used in order to offer new therapeutic approaches in the clinical workout of seminoma.
精原细胞瘤是最常见的睾丸生殖细胞肿瘤（TGCT）类型，占年轻男性肿瘤诊断的50%，而非精原细胞瘤占40%，混合形式占10%。目前认为TGCT由癌的原位癌（CIS）前体阶段发展而来。八聚体结合转录因子4（OCT4）对干细胞的自我更新至关重要。它被认为是细胞多能性的主要调节因子。先前的研究表明精原细胞瘤表达OCT4。转录因子Krüppel样因子4（KLF4）也与胚胎干细胞的维持有关。最后，我们之前证明了PTTG1在CIS和精原细胞瘤中的表达。在这项初步研究中，我们比较了PTTG1与KLF4和OCT4在精原细胞瘤中的联合表达，以验证我们的假设，即PTTG1标记肿瘤组织中特定的干细胞群体，与肿瘤密切相关。收集了5例因精原细胞瘤接受睾丸切除术患者的福尔马林固定石蜡包埋睾丸组织，并使用兔单克隆PTTG-1抗体和小鼠单克隆OCT4或小鼠单克隆KLF4抗体进行免疫荧光分析。在精原细胞瘤中，我们观察到所有精原细胞瘤以及精原细胞瘤的小管内区域的肿瘤细胞都强烈表达OCT-4。在许多肿瘤细胞中观察到KLF-4的表达。PTTG1标记一些特定的OCT4和KLF4阳性肿瘤细胞，主要位于肿瘤周边。在小管间浸润区域观察到同时表达OCT4/KLF4和PTTG1的细胞巢。这是首次在精原细胞瘤中鉴定出以OCT4、KLF4和PTTG1阳性细胞为特征的细胞群体，与癌症侵袭性相关。需要进一步研究以阐明是否可以通过PTTG1的功能消除来为精原细胞瘤的临床治疗提供新的治疗方法。
