Endocrine Abstracts

Introduction: Chemokines and their receptors (CR) have been demonstrated to be involved in tumour growth and site specific metastasis. Furthermore, several cytokines have been described to modulate adrenocortical function. Therefore, we have investigated the expression pattern and functional activity of chemokine receptors and of corresponding chemokines in adrenocortical tissue.

Methods: Chemokine and CR expression was assessed by RT-PCR in normal adrenals (NAG), NCI-h295-cells, SW13-cells and adrenocortical carcinomas (ACC). CXCR4-expression levels were quantified by qPCR and immunohistochemistry in 7 NAG, 23 benign adrenocortical tumours and 167 ACC tissues (135 primary tumours, 14 metastases and 18 local recurrencies). Effects of the CXCR4 ligand CXCL12 on hormone production and signal transduction in NCI-h295-cells was assessed by radioimmunoassay and western blot, respectively.

Results: The adrenal gland expresses multiple chemokine receptors (CXCR1-6,CCR1,2,5-9,11 and CX3CR1) and chemokines (CXCL1,3,8,12 and CCL22). CXCR4 was most abundantly detected in both NAG and in adrenocortical tumours. CXCL12 led to activation of the ERK signal cascade and slightly but significantly decreased cortisol production in NCI-h295-cells. Immunohistochemistry revealed positive CXCR4 staining mainly in the outer adrenocortical zone. Conn and Cushing adenomas showed highest expression levels compared to NAG, whereas non secreting adenomas had only weak CXCR4 expression. In ACC, CXCR4 expression levels showed considerable variation with highest levels in metastases and lowest in local recurrencies.

Conclusion: Chemokines and CR are expressed both in benign and neoplastic adrenal tissue. CXCR4 is one of the most abundant CR exhibiting functional activity in NCI-h295-cells. CXCR4 expression was significantly higher in endocrine active compared to inactive tumours, suggesting that CXCR4 plays a role in adrenal steroidogenesis. However, no significant differences in expression levels between benign and malignant tumours were detected.