Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and -218

Mol Cell Biochem. 2017 Mar;427(1-2):177-185. doi: 10.1007/s11010-016-2909-5. Epub 2016 Dec 30.

Abstract

Gliomas are the most common type of malignant primary brain tumors. Some treatments of gliomas exist, but they are rarely curative. Mesenchymal stem cells (MSCs) are emerging as potential modes of targeted cancer therapy owing to their capacity for homing toward tumor sites. It has been proposed that MSCs derived from various sources, such as bone marrow, adipose tissue and umbilical cord blood, can be used as cell-based therapy for brain tumors. Here, MSCs obtained from the synovial fluid of osteoarthritis or rheumatoid arthritis patients were investigated as therapeutic candidates. Specifically, we compared migratory and adhesive abilities, as well as expression levels of related genes and microRNA in bone marrow derived-MSCs (BMMSCs), adipose derived-MSCs (ADMSCs), and synovial fluid derived-MSCs (SFMSCs) after treatment with conditioned medium from gliomas. Migration and adhesion of SFMSCs increased through upregulation of the activated lymphocyte cell adhesion molecule (ALCAM) and N-cadherin by microRNA-192 and -218 downregulation, similar to BMMSCs and ADMSCs. Migratory capacities of all types of MSCs were evaluated in vivo, and SFMSCs migrated intensively toward gliomas. These results suggest that SFMSCs have potential for use in cell-based antitumor therapies.

Keywords: Activated lymphocyte cell adhesion molecule; N-Cadherin; Synovial fluid derived-mesenchymal stem cells; Tumor tropism; microRNA-192; microRNA-218.

MeSH terms

  • Antigens, CD / metabolism*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / therapy
  • Cadherins / metabolism*
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Line, Tumor
  • Cell Movement*
  • Female
  • Fetal Proteins / metabolism*
  • Glioma / metabolism
  • Glioma / therapy
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / biosynthesis*

Substances

  • ALCAM protein, human
  • Antigens, CD
  • CDH2 protein, human
  • Cadherins
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins
  • MIRN192 microRNA, human
  • MIRN218 microRNA, human
  • MicroRNAs