Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Cancer metastasis chemoprevention prevents circulating tumour cells from germination

“…Blastocyst implantation is a complex process including attachment of the blastocyst to the receptive endometrium and invasion of the trophoblastic cells of the conceptus into the endometrium and basement membrane. 189 After analysing the molecular and cellular similarities and differences between embryonic implantation to uterine endometrium and breast CTC adhesion to vascular endothelium, 190 we found that many biological factors were shared by both the embryonic implantation system and CTC adhesion-invasion system, including integrins, cellular adhesion molecules (CAM), such as EpCAM, ICAM, VCAM, and selectin, hormone receptors, sialyl Lewis X and MMPs. 112 The in vivo inhibition by abortifacients of both embryo implantation to uterus and CTC metastasis to lung further revealed similarities in molecular and cellular embedding between the reproduction system and cancer metastases, and provided fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs in vivo.…”

Correction to: Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention

“…Following publication of the original article [ 1 ], an error was found in the Author’s contributions section. The correct details should read as:…”