Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

Exp Cell Res. 2016 Jul 15;345(2):190-8. doi: 10.1016/j.yexcr.2016.06.003. Epub 2016 Jun 22.

Abstract

Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC was observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes.

Keywords: ALDH; CD133; Lung cancer stem cells; Mesenchymal stromal cells; Tumor xenografts; Wharton's jelly.

MeSH terms

  • Adenocarcinoma / pathology
  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle / drug effects
  • Cell Proliferation
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Humans
  • Lung Neoplasms / classification*
  • Lung Neoplasms / pathology*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mice, Inbred NOD
  • Mice, SCID
  • Microscopy, Fluorescence
  • Neoplastic Stem Cells / pathology*
  • Phenotype
  • Subcutaneous Tissue / pathology
  • Wharton Jelly / cytology*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Culture Media, Conditioned