Interleukin-4 Induces a CD44 high /CD49b high PC3 Subpopulation With Tumor-Initiating Characteristics

J Cell Biochem. 2018 May;119(5):4103-4112. doi: 10.1002/jcb.26607. Epub 2018 Jan 19.

Abstract

Pro- and anti-inflammatory cytokines may influence proliferation, migration, invasion, and other cellular events of prostate cancer (PCa) cells. The hyaluronan receptor CD44, which is regulated by Interleukin (IL)-4, is a prostate basal cell marker. CD44high /CD49bhigh expressing cells have been demonstrated to have tumor-initiating characteristics. Here, we aimed to analyze the effects of long-term IL-4 treatment on CD44/CD49b expression, migration, proliferation, and clonogenic potential of basal-like PCa cells. To this end PC3 cells were treated over 30 passages with 5 ng/mL IL-4 (PC3-IL4) resulting in an increased population of CD44high expressing cells. This was concurrent with a clonal outgrowth of cuboid-shaped cells, with increased size and light absorbance properties. Flow cytometry revealed that the PC3-IL4 CD44high expressing subpopulation corresponds to the CD49bhigh population. Isolation of the PC3-IL4 CD44high /CD49bhigh subpopulation via fluorescence-associated cell sorting showed increased migrative, proliferative, and clonogenic potential compared to the CD44low /CD49blow subpopulation. In conclusion, IL-4 increases a PC3 subpopulation with tumor-initiating characteristics. Thus, IL-4, similar to other cytokines may be a regulator of tumor-initiation and hence, may present a suitable therapy target in combination with current treatment options.

Keywords: basal cells; cancer stem cells; cytokine; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Humans
  • Hyaluronan Receptors / biosynthesis*
  • Integrin alpha2 / biosynthesis*
  • Interleukin-4 / metabolism*
  • Male
  • Neoplasm Proteins / metabolism*
  • PC-3 Cells
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • IL4 protein, human
  • Integrin alpha2
  • Neoplasm Proteins
  • Interleukin-4