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首页> 外文期刊>Journal of experimental & clinical cancer research : >Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention
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Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention

机译：嵌入胚胎和循环肿瘤细胞之间的相似性：用于癌症转移化学普通的中转化的基本原理

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The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17β-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17β-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.
机译：全球流行病学研究报告说，长期使用避孕药后，癌症风险降低。我们的系统研究表明，脱脂剂有效地防止通过循环肿瘤细胞（CTC）诱导的癌症转移。然而，厌流性预防CTC基癌转移的分子和细胞机制几乎未知。本研究旨在跨学科探讨胚胎植入和癌细胞粘附/侵袭之间的相似性和差异。在播种胚胎JEG-3和癌症MCF-7细胞上的生物标志物表达，以及嵌入子宫子宫内膜RL95-2和血管内皮HUVECS细胞，并在用17β-雌二醇加上孕酮和脱氮后进行处理。研究了口服甲基酮和米非司酮对正常雌性小鼠胚胎植入的影响及循环肿瘤细胞（CTCs）的刺痛/侵袭。胚胎JEG-3和癌症MCF-7细胞都表达了高SELX，CD47，凸轮，而子宫内膜RL95-2和内皮HUVECS均表现出高端和ICAM-1。近17β-雌二醇加上孕酮的近期生理浓度促进了通过上调整联蛋白和MMPS促进了JEG-3和MCF-7细胞的迁移和侵袭。然而，米非司酮和Metapristone显着抑制JEG​​-3和MCF-7细胞的迁移和侵袭，并分别抑制JEG​​-3和MCF-7对基质胶，RL95-2细胞和Huvecs的粘附性。通过分别下调Slex，MMP和MCF-7细胞，分别在RL95-2细胞和HUVEC中下调整合蛋白来实现抑制。 MIFEPRISTOTE和Metapristone显着抑制小鼠中的胚胎植入和癌细胞转移。两种系统之间的相似性提供了脱毛剂的基本原理，以将CTC粘附/侵入到远处转移器官中。目前的研究提供了对安全有效的癌症转移化学预防措施来重新测量的理由。

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