Constitutive secretion of Interleukin-4 dictates CD133+ side population cells to resist drug treatment and cell death

J BUON. 2015 Sep-Oct;20(5):1350-9.

Abstract

Purpose: In the present study, we made an attempt to elucidate the role of oversecretion of interleukin-4 (IL-4) in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC).

Methods: HNSCC samples were analyzed for the presence of CSCs by flow cytometry. In addition, we have performed drug and apoptosis resistance assays to determine the role of IL-4 in CSCs.

Results: HNSCC samples contained 3.3% of CD133+ cancer stem like side population (SP) cells in HNSCC which displayed infinite cell proliferation and they had high self-renewal capacity. These CD133+ cells displayed enhanced expression of IL-4, which promoted multidrug and apoptosis resistance. After neutralizing IL-4, the CD133+ SP cells became more sensitive to drug treatment and apoptosis.

Conclusions: Our data suggest that the autocrine secretion of IL-4 is a potential target for the development of novel anticancer drugs to prevent the CSCs-mediated therapy failure and tumorigenesis.

MeSH terms

  • AC133 Antigen
  • Antigens, CD / analysis*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Glycoproteins / analysis*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Interleukin-4 / physiology*
  • Neoplastic Stem Cells / pathology*
  • Peptides / analysis*
  • Side-Population Cells / pathology*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • IL4 protein, human
  • PROM1 protein, human
  • Peptides
  • Interleukin-4