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

Autor: Drebert Z; Laboratory of Experimental Cancer Research, Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., De Vlieghere E; Laboratory of Experimental Cancer Research, Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Bridelance J; Molecular Signaling and Cell Death Unit, VIB Center for Inflammation Research, Ghent University, Ghent, Belgium., De Wever O; Laboratory of Experimental Cancer Research, Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., De Bosscher K; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Receptor Research Laboratories, Nuclear Receptor Lab, VIB Center for Medical Biotechnology, Department of Biochemistry, Ghent University, Ghent, Belgium., Bracke M; Laboratory of Experimental Cancer Research, Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Beck IM; Laboratory of Experimental Cancer Research, Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department Health Sciences, Odisee University College, Ghent, Belgium. Electronic address: Ilse.Beck@odisee.be.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2018 Jan 15; Vol. 362 (2), pp. 332-342. Date of Electronic Publication: 2017 Nov 28.
DOI: 10.1016/j.yexcr.2017.11.034
Abstrakt: Cancer-associated fibroblasts (CAFs) support cancer growth, invasion, and metastasis. Glucocorticoids (GCs), drugs often administered together with chemotherapy, are steroidal ligands of the glucocorticoid receptor (GR), a transcription factor which upon activation regulates expression of multiple genes involved in suppression of inflammation. We have previously shown that in dexamethasone (Dex)-treated CAFs derived from colon cancer, production and secretion of several factors related to cancer progression, such as tenascin C (TNC) and hepatocyte growth factor (HGF), were strongly suppressed. In this study we show that GCs can neutralize the cancer cell-promoting properties of CAFs. Conditioned medium from solvent-treated CAFs (CM CTRL ) stimulates proliferation, motility and stretched morphotype of GR-deficient HCT8/E11 colon cancer cells. Yet, HCT8/E11 proliferation and stretched morphotype are impaired upon treatment with conditioned medium from Dex-treated CAFs (CM DEX ), but HCT8/E11 cell migration is slightly increased under these conditions. Moreover, expression and potential activity of MMP-2 is also reduced in CM DEX compared with CM CTRL . These combined in vitro results concur with the results from in vivo chick chorioallantoic membrane assays, where the co-cultures of CAFs with colon cancer cells displayed impaired tumor formation and cancer cell invasion due to Dex administration. Combined, GC treatment influences cancer cell behavior indirectly through effects on CAFs.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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