Expression of the chemokine receptor CXCR2 in normal and neoplastic neuroendocrine cells

Background-Chemokines effect their proinflammatory and growth regulatory ro les through interaction with serpentine receptors. One such receptor, CXCR2 , binds multiple CXC chemokines, including interleukin 8, GRO-alpha,, CRO-b eta, GRO-gamma, and NAP-2, We have previously identified CXCR2 expression o n myeloid cells, notably mature granulocytes, and projection neurons. Objective.-To determine the expression of CXCR2 by cells of the neuroendocr ine system. Design,Archival specimens from normal neuroendocrine tissues and their mali gnant counterparts were analyzed by immunohistochemistry with monoclonal an tibodies specific for CXCR1 and CXCR2. Results-Immunohistochemical analysis revealed high-level expression of CXCR 2 by cells in the pituitary, adrenal medulla, pancreatic islets, thyroid C cells, scattered Kulchitsky cells in the bronchi, and counterpart neuroendo crine cells in the stomach, small bowel, colon, and appendix. Neuroendocrin e neoplasms that demonstrated high-level CXCR2 expression included (1) prim ary carcinoids localized to the stomach, small bowel, colon, appendix, fall opian tube, ovary, and lung; (2) atypical carcinoids of the lung; (3) metas tatic carcinoids; (4) pituitary adenomas; (5) pheochromocytomas; and (6) me dullary carcinomas of the thyroid. Small cell lung carcinomas, large cell n euroendocrine carcinomas of the lung, small cell carcinoma of the cervix, M erkel cell carcinomas, neuroblastomas, and malignant melanomas lacked evide nce of CXCR2 expression. Conclusions-The expression of CXCR2 by normal neuroendocrine cells and neop lastic counterparts that have retained phenotypic features of this differen tiation program suggests that chemokines may play an important role in func tions that are characteristic of this cell type. In addition, this raises t he possibility that chemokines may modulate secretion of biologically activ e products of these cells and their neoplastic counterparts.