Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67000, Strasbourg, France.
Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67000, Strasbourg, France; SMPMS-INCI, Mass Spectrometry Facilities of the CNRS UPR3212, Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67000, Strasbourg, France.
Cancer Lett. 2022 Jan 1;524:232-244. doi: 10.1016/j.canlet.2021.10.009. Epub 2021 Oct 9.
Increasingly common, neuroendocrine tumors (NETs) are regarded nowadays as neoplasms potentially causing debilitating symptoms and life-threatening medical conditions. Pheochromocytoma is a NET that develops from chromaffin cells of the adrenal medulla, and is responsible for an excessive secretion of catecholamines. Consequently, patients have an increased risk for clinical symptoms such as hypertension, elevated stroke risk and various cardiovascular complications. Somatostatin analogues are among the main anti-secretory medical drugs used in current clinical practice in patients with NETs. However, their impact on pheochromocytoma-associated catecholamine hypersecretion remains incompletely explored. This study investigated the potential efficacy of octreotide and pasireotide (SOM230) on human tumor cells directly cultured from freshly resected pheochromocytomas using an implemented catecholamine secretion measurement by carbon fiber amperometry. SOM230 treatment efficiently inhibited nicotine-induced catecholamine secretion both in bovine chromaffin cells and in human tumor cells whereas octreotide had no effect. Moreover, SOM230 specifically decreased the number of exocytic events by impairing the stimulation-evoked calcium influx as well as the nicotinic receptor-activated inward current in human pheochromocytoma cells. Altogether, our findings indicate that SOM230 acts as an inhibitor of catecholamine secretion through a mechanism involving the nicotinic receptor and might be considered as a potential anti-secretory treatment for patients with pheochromocytoma.
神经内分泌肿瘤（NET）现在越来越常见，被认为是可能导致衰弱症状和危及生命的疾病的肿瘤。嗜铬细胞瘤是一种起源于肾上腺髓质嗜铬细胞的 NET，其特征是儿茶酚胺的过度分泌。因此，患者有发生临床症状的风险，如高血压、中风风险增加和各种心血管并发症。生长抑素类似物是目前 NET 患者临床实践中主要的抗分泌药物之一。然而，它们对嗜铬细胞瘤相关儿茶酚胺分泌过多的影响仍未得到充分探索。本研究使用实施的碳纤维安培法测定儿茶酚胺分泌，直接在从新鲜切除的嗜铬细胞瘤培养的人肿瘤细胞中研究了奥曲肽和帕瑞肽（SOM230）的潜在疗效。SOM230 治疗有效抑制了尼古丁诱导的牛嗜铬细胞瘤细胞和人肿瘤细胞中的儿茶酚胺分泌，而奥曲肽没有作用。此外，SOM230 通过损害刺激诱发的钙内流以及烟碱受体激活的内向电流特异性减少人嗜铬细胞瘤细胞中的胞吐事件数量。总之，我们的研究结果表明，SOM230 通过涉及烟碱受体的机制作为儿茶酚胺分泌的抑制剂起作用，并且可以被认为是嗜铬细胞瘤患者的潜在抗分泌治疗。
