Obstetrics and Gynecology Hospital, Fudan University, Postal address: 413 Zhaozhou Road, Shanghai, 200011, China.
Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Ruijin Second Road, Shanghai, 200025, China.
BMC Cancer. 2020 Sep 3;20(1):845. doi: 10.1186/s12885-020-07350-x.
Endometrial cancer, one of the most common malignant tumors, is a serious threat to women's health. Endometrial hyperplasia is a precursor of endometrial cancer. S100 calcium binding protein P (S100P) has been found to play important roles in many types of cancer. The present study aimed to investigate the expression of S100P in endometrial cancer and its precursor lesions, and to explore the possible mechanisms.
We collected paraffin sections of normal endometrium, simple and complex non-atypical hyperplasia, atypical hyperplasia, and endometrioid carcinoma. The expression of S100P in endometrial cancer and its precancerous lesions was observed using immunohistochemistry. We also cultured primary endometrial cells and endometrial cancer cell lines (Ishikawa and RL95-2), and observed the expression of S100P in these cells. Laser confocal microscopy was used to observe the co-localization of S100P and its interacting protein Ezrin in RL95-2 cells. We employed lentiviruses to knockdown and overexpress S100P and then detected the F-actin distribution and cell invasion using phalloidin staining and Transwell assays.
There was a gradual increase in the S100P signal as the disease progressed from normal endometrium and simple non-atypical hyperplasia, to complex non-atypical hyperplasia, atypical hyperplasia, and then to endometrial cancer. S100P was mainly distributed in the cytoplasm and co-localized with Ezrin in endometrial cancer cells. After knocking down S100P, F-actin aggregated in the nucleus or to the local cell membrane. Furthermore, knockdown of S100P in Ishikawa cells decreased their cell invasion capability. Meanwhile, S100P overexpression in endometrial stromal cells increased cell invasion.
These data suggested that S100P might be involved in the occurrence and development of endometrial cancer via interaction with Ezrin and re-organization of F-actin to promote cell invasion.
子宫内膜癌是最常见的恶性肿瘤之一，严重威胁着女性的健康。子宫内膜增生是子宫内膜癌的前驱病变。S100 钙结合蛋白 P（S100P）在多种类型的癌症中发挥着重要作用。本研究旨在探讨 S100P 在子宫内膜癌及其前驱病变中的表达，并探讨其可能的机制。
我们收集了正常子宫内膜、单纯和复杂非典型增生、不典型增生和子宫内膜样癌的石蜡切片。采用免疫组织化学法观察 S100P 在子宫内膜癌及其前驱病变中的表达。我们还培养了原代子宫内膜细胞和子宫内膜癌细胞系（Ishikawa 和 RL95-2），观察 S100P 在这些细胞中的表达。激光共聚焦显微镜观察 RL95-2 细胞中 S100P 与其相互作用蛋白 Ezrin 的共定位。我们采用慢病毒分别敲低和过表达 S100P，然后通过鬼笔环肽染色和 Transwell 实验检测 F- 肌动蛋白的分布和细胞侵袭。
随着疾病从正常子宫内膜和单纯非典型增生进展到复杂非典型增生、不典型增生，再到子宫内膜癌，S100P 信号逐渐增强。S100P 主要分布在细胞质中，在子宫内膜癌细胞中与 Ezrin 共定位。敲低 S100P 后，F-肌动蛋白聚集在细胞核或局部细胞膜。此外，Ishikawa 细胞中 S100P 的敲低降低了其细胞侵袭能力。同时，子宫内膜基质细胞中 S100P 的过表达增加了细胞侵袭。
这些数据表明，S100P 可能通过与 Ezrin 相互作用并重新组织 F-肌动蛋白来促进细胞侵袭，从而参与子宫内膜癌的发生和发展。
