Hambach Lena, Gallwas Julia, Gründker Carsten
Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany.
Department of Gynecology and Obstetrics, University Medical Center Göttingen, Göttingen, Germany
Cancer Genomics Proteomics. 2025 May-Jun;22(3):397-414. doi: 10.21873/cgp.20509.
BACKGROUND/AIM: Cervical cancer (CC) is the fourth most common cancer in women worldwide. There are two main histological subtypes of CC: the more common cervical squamous cell carcinoma (CSCC) and the rarer cervical adenocarcinoma (CAC), which has a poorer prognosis. Unlike estrogen receptor (ER) α and ERβ, G-protein-coupled estrogen receptor 1 (GPER1) is recognized as a rapid mediator of cellular estrogenic action and tends to have tumor suppressive properties in CC. Since a clinical study showed that an elevated GPER1 expression is associated with a worse prognosis, we investigated the effects of stable GPER1 overexpression (GPER1-OE) on SiHa CSCC and HeLa CAC cells.
SiHa CSCC and HeLa CAC cells with stable GPER1-OE were generated. GPER1-OE was tested by RT-qPCR, western blot and fluorescence-activated cell analysis (FACS). The effects of GPER1-OE on proliferation, migration, invasion, apoptosis and stem cell properties (colony and sphere formation) were then examined.
Successful GPER1-OE in SiHa CSCC and HeLa CAC cells was confirmed. The cell characterization experiments showed that SiHa CSCC cells with stable GPER1-OE had faster proliferation and migration, and increased stem cell properties with larger and more numerous colonies and larger tumor spheres. In HeLa CAC cells, on the other hand, GPER1-OE resulted in slower cell proliferation, migration and invasion, reduced colony formation and tumor sphere formation. An increased rate of apoptosis was also observed.
GPER1-OE resulted in a more aggressive tumor behavior of SiHa CSCC cells and a less aggressive tumor behavior of HeLa CAC cells, due to a different effect of GPER1 overexpression depending on the respective histological subtypes of CC. This underlines the need for personalized medicine and a precise differentiation of subtypes in CC-related research.
背景/目的：宫颈癌（CC）是全球女性中第四大常见癌症。CC主要有两种组织学亚型：较常见的宫颈鳞状细胞癌（CSCC）和较罕见的宫颈腺癌（CAC），后者预后较差。与雌激素受体（ER）α和ERβ不同，G蛋白偶联雌激素受体1（GPER1）被认为是细胞雌激素作用的快速介质，在CC中往往具有肿瘤抑制特性。由于一项临床研究表明GPER1表达升高与预后较差有关，我们研究了稳定过表达GPER1（GPER1-OE）对SiHa CSCC细胞和HeLa CAC细胞的影响。
构建了稳定过表达GPER1的SiHa CSCC细胞和HeLa CAC细胞。通过逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法和荧光激活细胞分析（FACS）检测GPER1-OE。然后检测GPER1-OE对细胞增殖、迁移、侵袭、凋亡和干细胞特性（集落和球体形成）的影响。
证实了在SiHa CSCC细胞和HeLa CAC细胞中成功实现了GPER1-OE。细胞特性实验表明，稳定过表达GPER1的SiHa CSCC细胞增殖和迁移更快，干细胞特性增强，形成更大、更多的集落和更大的肿瘤球体。另一方面，在HeLa CAC细胞中，GPER1-OE导致细胞增殖、迁移和侵袭减慢，集落形成和肿瘤球体形成减少。还观察到凋亡率增加。
由于GPER1过表达对CC各自组织学亚型的影响不同，GPER1-OE导致SiHa CSCC细胞的肿瘤行为更具侵袭性，而HeLa CAC细胞的肿瘤行为侵袭性较小。这凸显了在CC相关研究中个性化医疗和精确区分亚型的必要性。
