ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro

Oncotarget. 2015 Dec 15;6(40):42687-703. doi: 10.18632/oncotarget.5883.

Abstract

Cancer stem cells (CSCs) are associated with cancer recurrence and metastasis. Prostate cancer cells often metastasize to the bone with a complex microenvironment of cytokines favoring cell survival. In this study, the cell stemness influence of a group of interleukins including IL-3, 6, 10, 11 and 24 on human prostate cancer cell lines LNCaP and PC-3 was explored in vitro. Sulforhodamine B(SRB) and 5-ethynyl-2'-deoxyuridine (EdU) assays were applied to examine the effect on cell proliferation, and wound healing and transwell assays were used for migration and invasion studies, in addition to colony formation, Western blotting and flowcytometry for the expression of stemness factors and chemotherapy sensitivity. We observed that ILs-3, 6 and 11 stimulated while ILs-10 and 24 inhibited the growth, invasion and migration of both cell lines. Interestingly, ILs-3, 6 and 11 significantly promoted colony formation and increased the expression of SOX2, CD44 and ABCG2 in both prostate cancer cell lines. However, ILs-10 and 24 showed the opposite effect on the expression of these factors. In line with the above findings, treatment with either IL-3 or IL-6 or IL-11 decreased the chemosensitivity to docetaxel while treatment with either IL-10 or IL-24 increased the sensitivity of docetaxel chemotherapy. In conclusion, our results suggest that ILs-3, 6 and 11 function as tumor promoters while ILs-10 and 24 function as tumor suppressors in the prostate cancer cell lines PC-3 and LNCaP in vitro, and such differences may attribute to their different effect on the stemness of PCa cells.

Keywords: CD44 and ABCG2; cancer stem cells; chemotherapy; cytokines; interleukin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Drug Resistance, Neoplasm / physiology*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • In Vitro Techniques
  • Interleukin-10 / metabolism
  • Interleukin-11 / metabolism
  • Interleukin-3 / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Male
  • Microscopy, Fluorescence
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*

Substances

  • IL10 protein, human
  • IL11 protein, human
  • IL3 protein, human
  • IL6 protein, human
  • Interleukin-11
  • Interleukin-3
  • Interleukin-6
  • Interleukins
  • interleukin-24
  • Interleukin-10