The chemokine SDF1/CXCL12: a novel autocrine/paracrine factor involved in pituitary adenoma development

The relevance of the chemokine/chemokine receptor system has broaden to several tissues. Besides their physiologic role as chemotactic cytokines in immune surveillance, it is now clear that chemokines are key players in several pathological processes such as inflammation, infection, and cancer. In particular the altered expression of SDF1/CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization and metastasization. CXCL12 and CXCR4 are widely expressed in central nervous system cells including hypotalamus and pituitary gland. Increasing evidence supports now the hypothesis that CXCL12 acts as a neuromodulatory activity on the hypothalamus/pituitary axis and is a regulatory molecule of pituitary function. Moreover, the differential expression of CXCL12 and CXCR4 in normal and tumor pituitary adenoma cells suggests their involvement in pituitary tumor development through autocrine/paracrine mechanisms leading to adenoma cell proliferation and hormone hypersecretion. Future studies focusing the pathways sustained by chemokines may help identify the tumor-initiating events and accordingly possible strategies may be developed targeting these pathways in human pituitary tumors.