Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response?

Cell Immunol. 2011;266(2):116-22. doi: 10.1016/j.cellimm.2010.09.005. Epub 2010 Sep 27.

Abstract

Immunomodulatory function of bone marrow derived mesenchymal stem cells in cancer has recently been investigated. But the resident mesenchymal stem cells as whole in cancer and in the breast cancer tissue have not been studied well. In the present work we isolated adipose derived stem cells (ASCs) from breast cancer and normal breast tissues to investigate the expressions of IL-4, IL-10 and transforming growth factor (TGF)-β1 in ASCs and to see if ASCs isolated from patients can modulate the regulatory molecules on peripheral blood lymphocytes. Our results showed that IL-10 and TGF-β1 have significantly higher mRNA expressions in ASCs isolated from breast cancer patients than those from normal individuals (P value <0.05). The culture supernatant of ASCs isolated from breast cancer patients with pathological stage III induced upregulation of the mRNA expression levels of IL-4, TGF-β1, IL-10, CCR4 and CD25 in PBLs. In addition, the percentage of CD4+CD25(high)Foxp3(+) T regulatory cells was increased in vitro. When the same culture supernatant was added to ASCs isolated from normal subjects augmentation of the mRNA expressions of IL-4, IL-10, IL-8, MMP2, VEGF and SDF-1 in normal ASCs was also observed. These data collectively conclude that resident ASCs in breast cancer tissue may have crucial roles in breast tumor growth and progression by inducing regulatory molecules and promoting anti-inflammatory reaction within the tumor microenvironment. Further investigation is required to see if the immune suppression induced by ASCs is an independent property from tumor cells or ASCs gain their immunosuppressive potential from malignant cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chemokine CXCL12 / analysis
  • Chemokine CXCL12 / metabolism
  • Female
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunomodulation*
  • Interleukin-10 / analysis
  • Interleukin-10 / biosynthesis*
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-4 / analysis
  • Interleukin-4 / biosynthesis*
  • Interleukin-8 / analysis
  • Interleukin-8 / immunology
  • Iran
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 2 / metabolism
  • Mesenchymal Stem Cells / immunology*
  • Middle Aged
  • Neoplasm Staging
  • Receptors, CCR4 / analysis
  • Receptors, CCR4 / immunology
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta1 / biosynthesis*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • CCR4 protein, human
  • CXCL12 protein, human
  • Chemokine CXCL12
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-8
  • Receptors, CCR4
  • Transforming Growth Factor beta1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • Interleukin-4
  • MMP2 protein, human
  • Matrix Metalloproteinase 2