preproenkephalin and Carcinoma

Functional evidence suggests that opioid peptides such as dynorphin are involved in the regulation of airway macrophage functions and of human cancer growth. However, anatomical evidence for components of a putative dynorphin network within lung cancer patients is scarce. Tissue from lung cancer patients was examined immunohistochemically for all components of a local dynorphin (DYN) network. Double immunofluorescence microscopy analysis revealed colocalization of the opioid precursor PDYN with its end-product DYN, and key processing enzymes prohormone convertases 1 and 2 and carboxypeptidase E, as well as the kappa-opioid receptor (KOR) within alveolar macrophages and cancerous cells in varying degrees among patients. Moreover, chromograninA-immunoreactive pulmonary neuroendocrine cells expressing DYN were close to substance P- and KOR-immunoreactive sensory nerves. Our findings give a first hint of a neuroanatomical basis for a peripheral DYN network, conceivably regulating pulmonary, immune and cell-proliferative functions within the human lung, most likely in a paracrine/autocrine fashion.

Topics: Aged; Biomarkers, Tumor; Bronchi; Carboxypeptidase H; Carcinoma; Dynorphins; Enkephalins; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Lung Neoplasms; Macrophages, Alveolar; Male; Microscopy, Fluorescence; Middle Aged; Neurotransmitter Agents; Proprotein Convertase 1; Proprotein Convertase 2; Protein Precursors; Receptors, Opioid, kappa; Respiratory Mucosa

A thyroid medullary carcinoma from a man with the multiple endocrine neoplasia syndrome Type IIB was examined for the presence of opioid peptides. The tumor contained peptides derived from all three opioid precursors: pro-opiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. The tissue concentrations of the various opioid peptides varied considerably. beta-Endorphin, a POMC-derived peptide, was present in concentrations between 9 to 12 pmoles/g tissue; 8 pmoles/g tissue of alpha-neo-endorphin, a pro-dynorphin-derived product, were seen, whereas the pro-enkephalin-associated peptides were present in much lower concentrations (0.6-2.1 pmoles/g tissue). Immunohistochemical studies showed scattered opioid-positive cells in the tumor tissue and in two other thyroid medullary carcinomas. These data demonstrate that malignant neuroendocrine tumors may contain peptides derived from all three families of the endogenous opioids.

Topics: Adult; Antibodies, Monoclonal; Carcinoma; Endorphins; Enkephalins; Humans; Male; Pro-Opiomelanocortin; Protein Precursors; Radioimmunoassay; Thyroid Neoplasms