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

Li,Tao; Zhang,Chunfu; Ding,Yanling; Zhai,Wei; Liu,Kui; Bu,Fan; Tu,Tao; Sun,Lingxian; Zhu,Wei; Zhou,Fangfang; Qi,Wenkai; Hu,Jiabo; Chen,Huabiao; Sun,Xiaochun

doi:10.3892/or.2015.4109

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

Authors:
- Tao Li
- Chunfu Zhang
- Yanling Ding
- Wei Zhai
- Kui Liu
- Fan Bu
- Tao Tu
- Lingxian Sun
- Wei Zhu
- Fangfang Zhou
- Wenkai Qi
- Jiabo Hu
- Huabiao Chen
- Xiaochun Sun
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Affiliations: School of Medicine, Jiangsu University, Jiangsu Key Laboratory of Clinical Laboratory Medicine, Zhenjiang, Jiangsu 212013, P.R. China, The Second People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China
Published online on: July 3, 2015 https://doi.org/10.3892/or.2015.4109
Pages: 1469-1477

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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.

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