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Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion via effects on cancer-associated

Zuzanna Drebert1, Elly De Vlieghere1, Jolien Bridelance2

  • 1Laboratory of Experimental Cancer Research, Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.

Experimental Cell Research
|December 3, 2017
PubMed

Insights

Glucocorticoids (GCs) neutralize cancer-promoting fibroblasts (CAFs) by suppressing factors that stimulate tumor growth. This GC-mediated suppression of CAFs inhibits colon cancer cell proliferation and invasion in vitro and in vivo.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Cancer-associated fibroblasts (CAFs) promote tumor progression, invasion, and metastasis.
  • Glucocorticoids (GCs) are anti-inflammatory drugs that bind to the glucocorticoid receptor (GR).
  • Previous studies showed GCs suppress pro-cancer factors like tenascin C (TNC) and hepatocyte growth factor (HGF) in colon CAFs.

Purpose of the Study:

  • To investigate the effect of GCs on the cancer cell-promoting properties of CAFs.
  • To determine how GC-treated CAFs influence the behavior of GR-deficient colon cancer cells.
  • To evaluate the impact of GC treatment on CAF-cancer cell co-cultures in vitro and in vivo.

Main Methods:

  • Treatment of colon CAFs with dexamethasone (Dex), a GC.
  • Collection of conditioned medium from treated and untreated CAFs.
  • Assessment of colon cancer cell proliferation, motility, and morphotype using conditioned media.
  • Analysis of MMP-2 expression and activity.
  • In vivo chick chorioallantoic membrane (CAM) assays with co-cultured CAFs and cancer cells.

Main Results:

  • Conditioned medium from Dex-treated CAFs (CMDEX) impaired proliferation and altered morphotype of GR-deficient colon cancer cells compared to control medium (CMCTRL).
  • HCT8/E11 cell migration was slightly increased by CMDEX, while MMP-2 expression and activity were reduced.
  • In vivo CAM assays showed impaired tumor formation and reduced cancer cell invasion in co-cultures treated with Dex.

Conclusions:

  • GCs neutralize the pro-tumorigenic functions of CAFs.
  • GC treatment indirectly influences cancer cell behavior by altering CAF properties.
  • GCs represent a potential therapeutic strategy to target the tumor microenvironment in colon cancer.
Keywords:
Cancer cell invasionCancer cell proliferationCancer-associated fibroblasts (CAFs)Colon cancerGlucocorticoids

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