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.
Highlights
The human prostate gland consists of a bilayer of two main epithelial cell types; basal and luminal cells, as well as a small population of neuroendocrine cells
We show that IL-4 treatment resulted in an increased cellular subpopulation demonstrating high CD44 expression in the PC3 basal-like prostate cancer (PCa) cell line
Long-term IL-4 treatment led to an increase of this population leading to the conclusion that IL-4 can trigger the growth of a PC3 subpopulation expressing basal- and cancer stem cell (CSC)-like markers
Summary
The human prostate gland consists of a bilayer of two main epithelial cell types; basal and luminal cells, as well as a small population of neuroendocrine cells. Prostate adenocarcinoma commonly has a luminal phenotype and has been diagnosed for some time by the absence of basal cells.[1] several studies have demonstrated that a small population of primitive malignant cells with a basal phenotype (characterized by CD44+, AR-, CD49f+, cytokeratins (CK) 5/14+, and p63+ markers) exist, which have the capacity to recapitulate tumors.[2,3,4,5]. We show that IL-4 treatment resulted in an increased cellular subpopulation demonstrating high CD44 expression in the PC3 basal-like PCa cell line These cells showed increased mobility, proliferation, and clonogenic potential compared with cells with a low CD44 expression
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