title: Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and suppress the growth of MCF-7 human breast cancer cells.
abstract: Although it has been reported that mesenchymal stem cells (MSCs) suppress tumor growth in vitro and in vivo, little is known about the underlying molecular mechanisms. We found that type I interferon is expressed in adipose tissue-derived stem cells (ASCs) cultured at high density, and ASCs and their conditioned medium (ASC-CM) suppress the growth of MCF-7 cells in vitro. Growth inhibition was amplified by glucose deprivation that resulted from high density culture of ASCs after 3days. The cytotoxic effect of the ASC-CM obtained from high density culture of ASCs was neutralized by anti-IFN-β antibody. STAT1 was phosphorylated in MCF-7 cells treated with ASC-CM, and JAK1/JAK2 inhibitor treatment decreased STAT1 phosphorylation. The cytotoxic effect of ASC-CM was reduced especially by JAK1 inhibitors in MCF-7 cells. Our findings suggest that ASCs cultured at high density express type I interferons, which suppresses tumor growth via STAT1 activation resulting from IFN-β secretion in MCF-7 breast cancer cells.
authors.affiliation: Department of General Surgery, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Ryu
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Oh
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea; Department of Internal Medicine, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.affiliation: Department of Plastic and Reconstructive Surgery, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Jiye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of General Surgery, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Joon Hyung
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Choi
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Ha Cheol
authors.initials: HC
authors.lastname: Shin
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of General Surgery, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea. Electronic address: bksgs@yonsei.ac.kr.
authors.forename: Keum Seok
authors.initials: KS
authors.lastname: Bae
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju, Republic of Korea. Electronic address: yweom@yonsei.ac.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Eom
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000172:deficiency; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D047428:Protein Kinase Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D016899:Interferon-beta; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D005947:Glucose
keywords: Adipose tissue-derived stem cells; Growth suppression; High density culture; IFN-β; MCF-7