Colon cancer cells produce immunoregulatory glucocorticoids

Sidler, D; Renzulli, P; Schnoz, C; Berger, B; Schneider-Jakob, S; Flück, C; Inderbitzin, D; Corazza, N; Candinas, D; Brunner, T (2011). Colon cancer cells produce immunoregulatory glucocorticoids. Oncogene, 30(21), pp. 2411-9. Basingstoke, UK: Nature Publishing Group 10.1038/onc.2010.629

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Glucocorticoids (GC) have important anti-inflammatory and pro-apoptotic activities. Initially thought to be exclusively produced by the adrenal glands, there is now increasing evidence for extra-adrenal sources of GCs. We have previously shown that the intestinal epithelium produces immunoregulatory GCs and that intestinal steroidogenesis is regulated by the nuclear receptor liver receptor homolog-1 (LRH-1). As LRH-1 has been implicated in the development of colon cancer, we here investigated whether LRH-1 regulates GC synthesis in colorectal tumors and whether tumor-produced GCs suppress T-cell activation. Colorectal cancer cell lines and primary tumors were found to express steroidogenic enzymes and regulatory factors required for the de novo synthesis of cortisol. Both cell lines and primary tumors constitutively produced readily detectable levels of cortisol, as measured by radioimmunoassay, thin-layer chromatography and bioassay. Whereas overexpression of LRH-1 significantly increased the expression of steroidogenic enzymes and the synthesis of cortisol, downregulation or inhibition of LRH-1 effectively suppressed these processes, indicating an important role of LRH-1 in colorectal tumor GC synthesis. An immunoregulatory role of tumor-derived GCs could be further confirmed by demonstrating a suppression of T-cell activation. This study describes for the first time cortisol synthesis in a non-endocrine tumor in humans, and suggests that the synthesis of bioactive GCs in colon cancer cells may account as a novel mechanism of tumor immune escape.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology > Cytopathology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Sidler, Daniel; Renzulli, Pietro; Berger, Barbara; Flück, Christa; Inderbitzin, Daniel; Corazza, Nadia; Candinas, Daniel and Brunner, Thomas

ISSN:

0950-9232

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

26 Apr 2017 02:25

Publisher DOI:

10.1038/onc.2010.629

PubMed ID:

21258413

Web of Science ID:

000291008000003

URI:

https://boris.unibe.ch/id/eprint/830 (FactScience: 200976)

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