Adipose MSCs Suppress MCF7 and MDA-MB-231 Breast Cancer Metastasis and EMT Pathways Leading to Dormancy via Exosomal-miRNAs Following Co-Culture Interaction.

Autor: Mohd Ali N; Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia., Yeap SK; Marine Biotechnology, China-ASEAN College of Marine Sciences, Xiamen University Malaysia Campus, Jalan Sunsuria, Bandar Sunsuria, Sepang, Selangor 43900, Malaysia., Ho WY; Faculty of Medicine and Health Sciences, University of Nottingham (Malaysia Campus), Semenyih 43500, Malaysia., Boo L; Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia., Ky H; Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, Can Tho 900100, Vietnam., Satharasinghe DA; Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya 20400, Sri Lanka., Tan SW; Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia., Cheong SK; Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.; Cryocord Sdn Bhd, Persiaran Cyberpoint Selatan, Cyberjaya 63000, Malaysia., Huang HD; School of Life and Health Sciences, Warshel Institute for Computational Biology, The Chinese University of Hong Kong, Shenzhen 518172, China., Lan KC; Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 30010, Taiwan., Chiew MY; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan., Ong HK; Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2020 Dec 24; Vol. 14 (1). Date of Electronic Publication: 2020 Dec 24.
DOI: 10.3390/ph14010008
Abstrakt: Globally, breast cancer is the most frequently diagnosed cancer in women, and it remains a substantial clinical challenge due to cancer relapse. The presence of a subpopulation of dormant breast cancer cells that survived chemotherapy and metastasized to distant organs may contribute to relapse. Tumor microenvironment (TME) plays a significant role as a niche in inducing cancer cells into dormancy as well as involves in the reversible epithelial-to-mesenchymal transition (EMT) into aggressive phenotype responsible for cancer-related mortality in patients. Mesenchymal stem cells (MSCs) are known to migrate to TME and interact with cancer cells via secretion of exosome- containing biomolecules, microRNA. Understanding of interaction between MSCs and cancer cells via exosomal miRNAs is important in determining the therapeutic role of MSC in treating breast cancer cells and relapse. In this study, exosomes were harvested from a medium of indirect co-culture of MCF7-luminal and MDA-MB-231-basal breast cancer cells (BCCs) subtypes with adipose MSCs. The interaction resulted in different exosomal miRNAs profiles that modulate essential signaling pathways and cell cycle arrest into dormancy via inhibition of metastasis and epithelial-to-mesenchymal transition (EMT). Overall, breast cancer cells displayed a change towards a more dormant-epithelial phenotype associated with lower rates of metastasis and higher chemoresistance. The study highlights the crucial roles of adipose MSCs in inducing dormancy and identifying miRNAs-dormancy related markers that could be used to identify the metastatic pattern, predict relapses in cancer patients and to be potential candidate targets for new targeted therapy.
Databáze: MEDLINE
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