合体细胞滋养层细胞外囊泡阻止母体恶性肿瘤侵袭及转移至胎儿相关机制研究  

Study on mechanism of syncytiotrophoblast extracellular vesicles preventing maternal malignant tumor invasion and metastasis to fetus

作　　者：张燕[1] 粟闵 陈婷婷[1] 程会贤 陈名园 王巍[1] Zhang Yan;Su Min;Chen Tingting;Cheng Huixian;Chen Mingyuan;Wang Wei(Department of Pathology,Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University),Ministry of Education,West China Second University Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China;Laboratory of Molecular Translational Medicine,Western Institute of Maternal and Child Medicine,West China Second University Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]四川大学华西第二医院病理科、出生缺陷与相关妇儿疾病教育部重点实验室,成都610041 [2]四川大学华西第二医院西部妇幼医学研究院-分子与转化医学实验室,成都610041

出　　处：《中华妇幼临床医学杂志（电子版）》2022年第1期40-46,共7页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：四川省科技厅应用基础项目(2019YJ0065)。

摘　　要：目的探讨合体细胞滋养层细胞外囊泡(STB-EV)阻止母体恶性肿瘤侵袭、转移至胎儿的相关机制。方法选择2015年6月,于四川大学华西第二医院进行剖宫产术分娩的1例妊娠合并宫颈癌(CCP)患者被肿瘤侵犯的胎盘组织为研究对象。宫颈癌细胞系SiHa细胞和人滋养层细胞系HTR-8细胞,均由本院西部妇幼医学研究院-分子与转化医学实验室馈赠。其中,本例CCP患者被肿瘤侵犯的胎盘组织制作组织切片后,于光学显微镜(×400)和电子显微镜(×2000)下,观察其组织形态学、STB-EV及合体细胞滋养层(STB)旁宫颈癌细胞自噬性死亡情况等;而SiHa细胞与HTR-8细胞培养后,用于Transwell迁移实验与细胞划痕实验。将SiHa与HTR-8细胞共培养,纳入研究组;单独培养的SiHa细胞,纳入对照组。对2组细胞进行Transwell迁移实验及细胞划痕实验,2组Transwell小室穿膜细胞数、细胞迁移率等比较,采用成组t检验。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。结果①对本例CCP患者被肿瘤侵犯的胎盘组织制作组织切片后,于光学显微镜(×400)下观察结果显示,与STB相邻宫颈癌细胞自噬性死亡、凋亡和固缩性坏死显著。电子显微镜(×2000)下观察结果显示,宫颈癌细胞累及胎盘绒毛组织时,STB分泌的STB-EV水平显著高于正常胎盘组织。②2组细胞Transwell迁移实验结果显示,研究组穿膜细胞数为(597.6±87.7)个/视野,显著低于对照组的(1358.4±203.0)个/视野,并且差异有统计学意义(t=14.490、P<0.001)。③2组细胞划痕实验结果显示,划痕后48 h时,研究组细胞迁移率为(26.6±3.8)%,显著低于对照组的(45.9±3.7)%,并且差异有统计学意义(t=3.122、P=0.035)。结论STB分泌的STB-EV可能参与母体肿瘤细胞广泛自噬性死亡,从而阻止母体肿瘤细胞侵袭胎盘、影响胎儿发育。Objective To explore the mechanism of syncytiotrophoblast extracellular vesicles(STB-EV)preventing maternal malignant tumor invasion and metastasis to fetus.Methods Placental tissue invaded by tumor of a pregnant woman with cervical cancer in pregnancy(CCP)who underwent cesarean section in West China Second University Hospital,Sichuan University in June 2015 was selected as research subject.Cervical cancer cell line SiHa cells and human trophoblast cell line HTR-8 cells were donated by the Laboratory of Molecular and Translational Medicine,Western Institute of Maternal and Child Medicine,West China Second University Hospital,Sichuan University.Placental tissue invaded by cervical cancer of this CCP patient was sectioned,and its histomorphology,STB-EV and autophagic death of cervical cancer cells adjacent to syncytiotrophoblast(STB),etc.were observed under optical microscope(×400)and electron microscope(×2000).SiHa cells and HTR-8 cells were cultured for Transwell migration assay and cell scratch test.Co-cultured SiHa cells and HTR-8 cells were included into study group,while SiHa cells cultured separately were included into control group.Transwell migration assay and cell scratch test were performed on two groups of cells to evaluate the interaction between HTR-8 and SiHa cells.Independent-samples t test was used to compare the number of transmembrane penetrating cells and cell mobility between two groups.The procedures followed in this study were in line with the newly revised World Medical Association Declaration of Helsinki in 2013.Results①Results of placental tissue invaded by cervical cancer of this CCP patients under optical microscope(×400)showed that autophagy death,apoptosis and pyknotic necrosis of cervical cancer cells adjacent to STB were significant.Electron microscopy(×2000)results showed that when cervical cancer cells involved placental villi,level of STB-EV secreted by STB was significantly higher than that in normal placental tissues.②Results of Transwell migration assay in two groups sh

关 键 词：滋养层 合体细胞滋养层细胞外囊泡 宫颈肿瘤 胎盘 妊娠并发症 肿瘤 孕妇 

分 类 号：R73[医药卫生—肿瘤]