Commentary on Chapters ‘Clinical and Developmental Aspects’ and ‘Stress Responses of the Adrenal Medulla’

Abstract

The division of the contributions to this volume into Chromogranins, Ion Channels, Secretion Mechanisms, Clinical and Developmental Aspects, and Stress Responses of the Adrenal Medulla is somewhat arbitrary: there is clearly much overlap among these domains of chromaffin cell research. This commentary covers both Clinical/ Developmental, and Stress Responses together, mainly to emphasize this overlap, and the translational importance of these two aspects of the chromaffin cell as a stress transducer. Genetics, development and stress were three topics of particular clinical relevance that were developed in depth through contributions presented at the 15th International Symposium for Chromaffin Cell Biology. The genetics of the chromaffin cell in normal physiology and disease were highlighted by contributions focusing on markers of chromaffin cell origin relevant to cancer including pheochromocytoma, and on catecholaminergic markers for hypertension and other cardiovascular diseases. Colon, pancreas, prostate and lung outrank the adrenal medulla as organs of medical concern in human cancer. Although pheochromocytoma, or cancer of adrenomedullary origin is rare, it is an important subject of study for several reasons. First, it arises from a limited and distinct set of cell types, and therefore is an attractive model for etiology of proliferative disease. Second, pheochromocytoma can be either metastatic, malignant or benign, and therefore can be used to search for markers to make this clinically crucial diagnosis. Murthy et al. propose carboxypeptidase E (CPE), the enkephalin prohormone processing enzyme first characterized in bovine chromaffin granules in 1982 (Hook et al., Nature 295:341–342, 1982), as such a marker. Meta-analysis of microarray expression data sets in the Gene Expression Omnibus (GEO) allowed Murthy and colleagues to identify CPE as a transcript frequently represented in the transcriptomes of metastatic cancers of both endocrine and epithelial origin. Thus, cervical, colorectal, renal, and bone (Ewing sarcoma), astrocytic, and oligodendroglial tumors or cells express higher levels of CPE mRNA than their non-cancerous cells and tissues of origin: in fact most of the corresponding cells of origin do not have appreciable concentrations of CPE. Lung, pituitary and pheochromocytoma tissue (i.e. neuroendocrine tumors) express higher CPE levels than their tissues of origin. Most significantly, metastatic pheochromocytoma expresses significantly higher CPE mRNA than benign. Should CPE prove a reliable prognostic marker for malignancy in pheochromocytoma and other neuroendocrine cancers, and perhaps even in non-endocrine cancers, its potential for translation to standard clinical practice would be high. Thouennon and Anouar report on expression of neuropeptides in pheochromocytoma that may be involved in trophic, proliferative and angiogenic paracrine/autocrine actions contributing to tumor growth. A strong correlation between NPY and PACAP expression was documented in 25 pheochromocytomas, and between RDC1, the adrenomedullin receptor, and VEGF, with angiogenic activity. These authors review the evidence for concerted expression This is a commentary to articles doi:10.1007/s10571-010-9535-7 10.1007/s10571-010-9567-z, 10.1007/s10571-010-9571-3, 10.1007/s10571-010-9578-9, 10.1007/s10571-010-9575-z, 10.1007/s10571-010-9582-0, 10.1007/s10571-010-9583-z, 10.1007/s10571-010-9592-y, 10.1007/s10571-010-9593-x, 10.1007/s10571-010-9594-9, 10.1007/s10571-010-9600-2, 10.1007/s10571-010-9606-9, 10.1007/s10571-010-9620-y.