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 cellula...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-09-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-02104-4 |
| _version_ | 1819153854664540160 |
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| author | Jie Wang Xiaobo Yu Huayi Peng Yusheng Lu Shuhui Li Qing Shi Jian Liu Haiyan Dong Vladimir Katanaev Lee Jia |
| author_facet | Jie Wang Xiaobo Yu Huayi Peng Yusheng Lu Shuhui Li Qing Shi Jian Liu Haiyan Dong Vladimir Katanaev Lee Jia |
| author_sort | Jie Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T15:11:48Z |
| format | Article |
| id | doaj.art-50867d0f54b4445a8aea9a681d390639 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-22T15:11:48Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-50867d0f54b4445a8aea9a681d3906392022-12-21T18:21:51ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-09-0140111610.1186/s13046-021-02104-4Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemopreventionJie Wang0Xiaobo Yu1Huayi Peng2Yusheng Lu3Shuhui Li4Qing Shi5Jian Liu6Haiyan Dong7Vladimir Katanaev8Lee Jia9College of Materials and Chemical Engineering, Minjiang UniversityCancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou UniversityFujian Provincial Key Laboratory of Inspection and Quarantine Technology Research/ Technology Center of Fuzhou CustomsCollege of Materials and Chemical Engineering, Minjiang UniversityCancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou UniversityCancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou UniversityCancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou UniversityFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical UniversityCollege of Materials and Chemical Engineering, Minjiang UniversityCollege of Materials and Chemical Engineering, Minjiang UniversityAbstract 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.https://doi.org/10.1186/s13046-021-02104-4Circulating tumor cellsCancer metastatic chemopreventionAbortifacientsEmbryo implantationAdhesion/invasion |
| spellingShingle | Jie Wang Xiaobo Yu Huayi Peng Yusheng Lu Shuhui Li Qing Shi Jian Liu Haiyan Dong Vladimir Katanaev Lee Jia Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention Journal of Experimental & Clinical Cancer Research Circulating tumor cells Cancer metastatic chemoprevention Abortifacients Embryo implantation Adhesion/invasion |
| title | Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention |
| title_full | Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention |
| title_fullStr | Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention |
| title_full_unstemmed | Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention |
| title_short | Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention |
| title_sort | embedding similarities between embryos and circulating tumor cells fundamentals of abortifacients used for cancer metastasis chemoprevention |
| topic | Circulating tumor cells Cancer metastatic chemoprevention Abortifacients Embryo implantation Adhesion/invasion |
| url | https://doi.org/10.1186/s13046-021-02104-4 |
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