Mesenchymal stem cell‑derived extracellular vesicles promote the in vitro proliferation and migration of breast cancer cells through the activation of the ERK pathway

Int J Oncol. 2019 May;54(5):1843-1852. doi: 10.3892/ijo.2019.4747. Epub 2019 Mar 13.

Abstract

Mesenchymal stem cells (MSCs) have been demonstrated to be involved in tumor progression and the modulation of the tumor microenvironment, partly through their secretome. Extracellular vesicles (EVs) are membranous nanovesicles secreted by multiple types of cells and have been demonstrated to mediate intercellular communication in both physiological and pathological conditions. However, numerous questions still remain regarding the underlying mechanisms and functional consequences of these interactions. The purpose of this study was to investigate the effects of human umbilical cord mesenchymal stem cell‑derived EVs (hUC‑MSC‑EVs) on the proliferation, migration and invasion of human breast cancer cells. We successfully generated and identified hUC‑MSCs and hUC‑MSC‑EVs which were used in this study. The results revealed that treatment of the MDA‑MB‑231 and MCF‑7 human breast cancer cells with medium containing hUC‑MSC‑EVs significantly enhanced the proliferation, migration and invasion of the cells in vitro. Treatment of the cells with medium containing hUC‑MSC‑EVs also reduced E‑cadherin expression and increased N‑cadherin expression, thus promoting the epithelial‑mesenchymal transition (EMT) of the breast cancer cells. Treatment of the breast cancer cells with extracellular signal‑regulated kinase (ERK) inhibitor prior to the interaction with hUC‑MSC‑EVs significantly reversed the enhanced proliferation, migration and invasion, as well as the EMT of the breast cancer cells induced by the hUC‑MSC‑EVs. On the whole, these data indicate that hUC‑MSC‑EVs promote the invasive and migratory potential of breast cancer cells through the induction of EMT via the ERK pathway, leading to malignant tumor progression and metastasis. Taken together, the findings of this study suggest that targeting pathways to reverse EMT may lead to the development of novel therapeutic approaches with which to combat breast cancer.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media / chemistry
  • Culture Media / pharmacology*
  • Epithelial-Mesenchymal Transition
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System* / drug effects
  • MCF-7 Cells
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Tumor Microenvironment
  • Umbilical Cord / cytology
  • Umbilical Cord / metabolism

Substances

  • Culture Media