Induction of thymic stromal lymphopoietin in mesenchymal stem cells by interaction with myeloma cells

Leuk Lymphoma. 2014 Nov;55(11):2605-13. doi: 10.3109/10428194.2014.881478. Epub 2014 Mar 7.

Abstract

Recently, the bone marrow (BM) microenvironment has been reported to support the survival of multiple myeloma (MM) cells. In this study, we examined changes in gene expression profile in human mesenchymal stem cells (MSCs) by co-culture with MM cells. cDNA array analysis indicated that co-culture induced multiple factors which have positive effects on the survival of MM cells, such as interleukin-6 (IL-6) and insulin-like growth factor-1. Other than these factors, thymic stromal lymphopoietin (TSLP), which is a cytokine involved in the progression of pancreatic and breast cancer through induction of T helper 2 cell responses, was up-regulated in MSCs. TSLP exhibited no effect on proliferation or drug resistance of MM cells, but TSLP secreted from MSCs by co-culture expanded IL-13+ CD4+ T cells through stimulation of dendritic cells. These results suggested that MM cells positively act to induce various molecules in MSCs, leading to the formation of a more advantageous BM microenvironment for their survival.

Keywords: Multiple myeloma; TSLP; microenvironment.

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Communication / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Dendritic Cells / metabolism
  • Humans
  • Interleukin-13 / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymic Stromal Lymphopoietin
  • Transcriptional Activation*
  • Transcriptome
  • Up-Regulation

Substances

  • Cytokines
  • Interleukin-13
  • Thymic Stromal Lymphopoietin