Ghanem G, Loir B, Morandini R, Sales F, Lienard D, Eggermont A, Lejeune F
LOCE, Institut J. Bordet, Free University of Brussels, Brussels, Belgium.
Int J Cancer. 2001 Nov;94(4):586-90. doi: 10.1002/ijc.1504.
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 melanoma serum marker. Within cells, S100B protein exists in homo- or heterodimer form containing mainly Ca(++), having a substantial fraction bound to membranes. As such, S100B is believed to be involved in the regulation of cytoskeleton. Also, a role in the cell cycle progression has been suggested. Although S100B appears having important intracellular functions, proofs of its secretion, at least at concentrations such as the ones measured in melanoma patients, are still lacking. Consistent with this view is the fact that immunohistology for S100 protein reported by numerous authors clearly indicate an exclusive intracellular staining. For these reasons, it was of a major interest to investigate how and when S100B is shed to the blood. Knowing that significant S100B levels are seen only in stage IV patients, we hypothesized 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 highly cytotoxic regional immunochemotherapy using isolated limb perfusion with tumor necrosis factor and melphalan, as well as in tumor exudates and pleural fluids. Our results strongly suggest melanoma and endothelial cell death 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.
目前这项工作的目的是研究内源性S100B蛋白的来源和半衰期，许多研究者将其报道为一种有用的黑色素瘤血清标志物。在细胞内，S100B蛋白以同二聚体或异二聚体形式存在，主要含有Ca(++)，有相当一部分与细胞膜结合。因此，S100B被认为参与细胞骨架的调节。此外，也有人提出它在细胞周期进程中发挥作用。尽管S100B似乎具有重要的细胞内功能，但仍缺乏其分泌的证据，至少在黑色素瘤患者所测浓度水平下的分泌证据仍然不足。许多作者报道的S100蛋白免疫组织化学结果清楚地表明其染色仅在细胞内，这一事实与上述观点一致。基于这些原因，研究S100B如何以及何时释放到血液中就显得尤为重要。鉴于仅在IV期患者中才观察到显著的S100B水平，我们推测细胞死亡可能是这些患者循环中S100B蛋白的主要来源。我们在一个模拟细胞死亡的体外模型中、在接受使用肿瘤坏死因子和马法兰进行离体肢体灌注的高细胞毒性区域免疫化疗的黑色素瘤及其他癌症患者体内、以及在肿瘤渗出液和胸水中对这一假设进行了研究。我们的结果有力地表明，黑色素瘤和内皮细胞死亡以及随后向血液的持续引流是S100B释放到血液循环背后的主要机制。我们估计内源性S100B蛋白的半衰期约为30分钟。
