Effect of tumor burden on tumor aggressiveness and immune modulation in prostate cancer: Association with IL-6 signaling

Chun Te Wu, Yun Ching Huang, Wen Cheng Chen, Miao Fen Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations

Abstract

Local treatment is known to improve survival in men with locally advanced prostate cancer (LAPC), but the underlying mechanisms remain unclear. In the present study, we examined the role of tumor burden in tumor aggressiveness, as well as the pathway responsible for these changes. We used human and murine prostate cancer cell lines to examine the role of tumor burden in tumor aggressiveness, as well as its correlation with cancer stem cell (CSC) marker levels and IL-6 signaling. Furthermore, 167 prostate cancer biopsy specimens were analyzed in terms of correlations of IL-6 and CD44 levels with clinical patient characteristics. Data from preclinical models showed that larger tumor burden was associated with more aggressive tumor growth associated and increased CD44 expression. Using cellular experiments and orthotopic tumor models, we showed that CD44+ prostate cancer cells have CSC-like properties, enhanced epithelial–mesenchymal transition (EMT), and a more immunosuppressive microenvironment. There was a significant correlation between IL-6 and CD44 levels based on in vitro testing of clinical samples. Blockade of IL-6/STAT3 signaling attenuated the expression of CD44, CSC-like properties, and aggressive tumor behavior in vitro and in vivo. In conclusion, CD44 expression is significantly associated with tumor aggressiveness in prostate cancer and activation of IL-6 signaling leads to a suitable microenvironment for the induction of CD44 expression. Based on our study, reduced tumor burden was associated with attenuated IL-6 signaling and augmented tumor rejection in the microenvironment, which might mediate the benefit of clinical adoption with aggressive local therapy.

Original languageEnglish
Article number992
JournalCancers
Volume11
Issue number7
DOIs
StatePublished - 07 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CD44
  • IL-6
  • Immune
  • Prostate cancer
  • Tumor burden

Fingerprint

Dive into the research topics of 'Effect of tumor burden on tumor aggressiveness and immune modulation in prostate cancer: Association with IL-6 signaling'. Together they form a unique fingerprint.

Cite this