On the release and half-life of S100B protein in the peripheral blood of melanoma patients

The aim of the present work was to investigate the origin and half-life of endogenous S100B protein reported by many investigators as a useful melanom a serum marker. Within cells, S100B protein exists in homo- or heterodimer form containing mainly Ca++, having a substantial fraction bound to membran es. As such, S100B is believed to be involved in the regulation of cytoskel eton. Also, a role in the cell cycle progression has been suggested. Althou gh SNOB appears having important intracellular functions, proofs of its sec retion, at least at concentrations such as the ones measured in melanoma pa tients, are still lacking. Consistent with this view is the fact that immun ohistology for S100 protein reported by numerous authors clearly indicate a n exclusive intracellular staining. For these reasons, it was of a major in terest to investigate how and when S100B is shed to the blood. Knowing that significant S100B levels are seen only in stage IV patients, we hypothesiz ed that cell death may be the major source of circulating S100B protein in these patients. This hypothesis was studied in an in vitro model simulating cell death and in vivo in melanoma and other cancer patients undergoing hi ghly cytotoxic regional immunochemotherapy using isolated limb perfusion wi th tumor necrosis factor and melphalan, as well as in tumor exudates and pl eural fluids. Our results strongly suggest melanoma and endothelial cell de ath and subsequent continuous drainage to the blood as the major mechanism behind S100B release to the blood circulation. We estimated the endogenous S100B protein half-life to be about 30 min. (C) 2001 Wiley-Liss, Inc.