Corticotropin-releasing factor facilitates cytokine and chemokine activation in the sarcoma-derived cell line, J774

Abstract Neuroendocrine factors found within the tumor microenvironment are considered targets for the regulation of carcinogenesis. Corticotropin releasing factor (CRF) and its receptors have recently been identified to have agonists and antagonist effects on various human tumors, however, its role in tumor immunology is still unclear. Immunological markers such as toll-like receptors (TLRs), cytokines and chemokines expressed by tumors and the tumor microenvironment can facilitate resistance against tumor development as well as promote tumor escape mechanisms. In the current study, we investigated the impact of CRF on TLR-2 and TLR-4 expression as well as its influence on the type of tumor cell associated cytokine (IL-1β, IL-6, TGF-β, IL-10) and chemokine (CCL3, CCL4, CCL17, CCL22, CXCL1, CXCL10) expression using quantitative real-time RT-PCR techniques. Our results demonstrate that CRF can elicit an induction of TLR-2 expression corresponding with IL-1β, and IL-6 cytokine and chemokines CCL3, CCL17 and CCL22. This report extends the potential role of CRF in modulation of the tumor microenvironment through regulation of tumor-associated immunological responses and raises the potential for CRF and its receptors as immunotherapeutic targets against carcinogenesis.