Interleukin‐4 induces a CD44(high)/CD49b(high) PC3 subpopulation with tumor‐initiating characteristics

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. CD44(high)/CD49b(high) 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 CD44(high) 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 CD44(high) expressing subpopulation corresponds to the CD49b(high) population. Isolation of the PC3‐IL4 CD44(high)/CD49b(high) subpopulation via fluorescence‐associated cell sorting showed increased migrative, proliferative, and clonogenic potential compared to the CD44(low)/CD49b(low) 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.