A role for paracrine interleukin-6 signaling in the tumor microenvironment in prostate tumor growth

Shu Han Yu, Janielle P. Maynard, Ajay M. Vaghasia, Angelo M. De Marzo, Charles G. Drake, Karen S. Sfanos

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Interleukin-6 (IL-6) is a mediator of inflammation that can facilitate prostate cancer progression. We previously demonstrated that IL-6 is present in the prostate tumor microenvironment and is restricted almost exclusively to the stromal compartment. The present study examined the influence of paracrine IL-6 signaling on prostate tumor growth using allograft models of mouse prostate cancer (TRAMP-C2), colon cancer (MC38), and melanoma (B16) cell lines in wildtype (WT) and IL-6 knockout (IL-6−/−) mice. Methods: Cells were implanted into WT or IL-6−/− mice and tumor sizes were measured at a 3 to 4 day interval. Serum, tumors, and other organs were collected for IL-6 analysis by ELISA and RNA in situ hybridization (RISH). Results: There was a significant reduction in TRAMP-C2 and B16 tumor size grown in IL-6−/− mice versus WT mice (P = 0.0006 and P = 0.02, respectively). This trend was not observed for the MC38 cell line. RISH analysis of TRAMP-C2 tumors grown in WT mice showed that cells present in the tumor microenvironment were the primary source of IL-6 mRNA, not the TRAMP-C2 cells. Serum IL-6 ELISA analyses showed an increase in the circulating levels of IL-6 in WT mice bearing TRAMP-C2 tumors. Similar phospho-STAT3 expression and tumor vascularization were observed in TRAMP-C2 tumors grown in WT and IL-6−/− mice. Conclusions: Our results are consistent with previous studies in prostate cancer patients demonstrating that paracrine IL-6 production in the tumor microenvironment may influence tumor growth. Additionally, these data provide evidence that elevated systemic IL-6 levels may be involved in tumor growth regulation in prostate cancer, and are not simply caused by or indicative of tumor burden.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalProstate
Volume79
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • inflammation
  • interleukin 6
  • microenvironment
  • prostate cancer
  • tumor growth

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint

Dive into the research topics of 'A role for paracrine interleukin-6 signaling in the tumor microenvironment in prostate tumor growth'. Together they form a unique fingerprint.

Cite this