Department of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, Germany.
Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
J Cell Biochem. 2018 May;119(5):4103-4112. doi: 10.1002/jcb.26607. Epub 2018 Jan 19.
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 /CD49b 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 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 expressing subpopulation corresponds to the CD49b population. Isolation of the PC3-IL4 CD44 /CD49b subpopulation via fluorescence-associated cell sorting showed increased migrative, proliferative, and clonogenic potential compared to the CD44 /CD49b 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.
促炎细胞因子和抗炎细胞因子可能影响前列腺癌 (PCa) 细胞的增殖、迁移、侵袭和其他细胞事件。透明质酸受体 CD44 受白细胞介素 (IL)-4 调节，是前列腺基底细胞的标志物。已经证明 CD44/CD49b 表达的细胞具有肿瘤起始特性。在这里，我们旨在分析长期 IL-4 治疗对基底样 PCa 细胞中 CD44/CD49b 表达、迁移、增殖和克隆形成潜力的影响。为此，我们用 5ng/mL IL-4（PC3-IL4）处理 PC3 细胞超过 30 代，导致表达 CD44 的细胞数量增加。这与立方体形细胞的克隆生长同时发生，这些细胞体积增大，光吸收特性增强。流式细胞术显示，PC3-IL4 中 CD44 表达的亚群与 CD49b 群体相对应。通过荧光激活细胞分选分离 PC3-IL4 CD44/CD49b 亚群，与 CD44/CD49b 亚群相比，具有更高的迁移、增殖和克隆形成潜力。总之，IL-4 增加了具有肿瘤起始特性的 PC3 亚群。因此，IL-4 与其他细胞因子类似，可能是肿瘤起始的调节剂，因此可能是与当前治疗选择相结合的合适治疗靶点。
