title: Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway.
abstract: Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues and to play an important role in cancer progression. However, the effects of MSCs on tumor progression remain controversial. The purpose of the present study was to detect the effects of human umbilical cord-derived MSCs (hUC‑MSCs) on the human breast cancer cell lines MDA-MB‑231 and MCF-7 in vitro and the underlying mechanisms. MSCs were isolated and identified from umbilical cord tissues. MDA-MB‑231 and MCF-7 cells were treated with conditioned medium (CM) from 10 and 20% umbilical cord MSCs (UC-MSCs), and the resulting changes in proliferation and migration were investigated. The 3-(4,5-dimethyl-2-thiazolyl)‑2,5-diphenyl‑2-H-tetrazolium bromide (MTT) and plate clone formation assays were used to assess the effect on proliferation, and the effects of CM on MDA-MB-231 and MCF-7 migration were assessed through scratch wound and Transwell migration assays. The expression of cell proliferation- and metastasis-related genes and proteins and activation of the ERK signaling pathway were analyzed by RT-PCR and western blot assays. UC-MSCs are characteristically similar to bone marrow MSCs (BM-MSCs) and exhibit multipotential differentiation capability (i.e., osteoblasts and adipocytes). The MTT, plate clone formation, scratch wound and Transwell migration assay results revealed that 10 and 20% CM promoted the proliferation and migration to higher levels than those observed in the control group. Our findings showed that UC-MSC-CM inhibited E-cadherin expression, increased the expression of N-cadherin and proliferating cell nuclear antigen (PCNA) and enhanced the expression of ZEB1, a transcription factor involved in epithelial‑to‑mesenchymal transition (EMT), through activation of the ERK pathway. U0126, an inhibitor of ERK, reversed the effects of UC-MSC-CM on breast cancer cell proliferation and migration. We conclude that UC-MSCs promote the proliferation and migration of breast cancer cell lines via activation of the ERK pathway.
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: The Second People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Ding
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Bu
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tu
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Lingxian
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Qi
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Hu
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Huabiao
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Sun
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D014470:Umbilical Cord / Q000166:cytology; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D017077:Culture Media, Conditioned; D018398:Homeodomain Proteins; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1