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首页> 外文期刊>Journal of dermatological science >Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells
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Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells

机译：血清素和电离辐射协同影响恶性黑色素瘤细胞的增殖和粘附分子表达

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摘要

Background: Mast cells are key effectors of the immune system and are involved in a variety of physiological and pathophysiological processes. Dermal mast cells have been demonstrated to degranulate as a consequence of ionizing radiation exposure. Mast cells accumulate at the periphery of skin tumours including malignant melanoma. Melanoma cells thus represent a potential target for the action of mediators released from irradiated mast cells. Objective: In this study, we evaluated the effects of serotonin and ionizing radiation on the proliferation and the adhesion molecule expression of malignant melanoma cells. Methods: Human mast cells (HMC-1) were examined for serotonin release after irradiation using an enzyme-linked immunosorbent assay (ELISA). Protein expression of serotonin receptors and adhesion molecules on human melanoma cells (IPC-298) was investigated by flow cytometry. Cell attachment to fibronectin was determined by an adhesion assay. Proliferation and cell cycle kinetics were analysed by proliferation assay and 5-bromodeoxyuridine (BrdU)/DNA dual parameter flow cytometry, respectively. Results: Ionizing radiation exposure resulted in serotonin release by HMC-1 cells. Expression of serotonin receptors was detected on IPC-298 cells. Serotonin enhanced the radiation-induced reduction in melanoma cell proliferation. Serotonin and ionizing radiation synergistically increased the expression of adhesion molecules on melanoma cells and improved cell adhesion to fibronectin. The up-regulation of cellular adhesion molecule expression was attenuated by inhibitors to phosphatidylinositol 3-kinase, mitogen-activated protein (MAP) ERK kinase and protein kinase C. Conclusions: Our data suggest that serotonin released from irradiated dermal mast cells modulates the radiation response of human melanoma cells. We postulate that radiation-induced mast cell degranulation and mediator release have a great impact on malignant melanoma cell development.
机译：背景：肥大细胞是免疫系统的关键效应物，参与多种生理和病理生理过程。真皮肥大细胞已证明由于电离辐射暴露而脱颗粒。肥大细胞聚集在包括恶性黑色素瘤在内的皮肤肿瘤的周围。因此，黑素瘤细胞代表了从辐射的肥大细胞释放的介体作用的潜在靶标。目的：在本研究中，我们评估了5-羟色胺和电离辐射对恶性黑色素瘤细胞增殖和粘附分子表达的影响。方法：使用酶联免疫吸附试验（ELISA）检测照射后人肥大细胞（HMC-1）的血清素释放。通过流式细胞术研究了血清素受体和粘附分子在人黑素瘤细胞（IPC-298）上的蛋白表达。通过粘附测定确定细胞与纤连蛋白的附着。通过增殖测定和5-溴脱氧尿苷（BrdU）/ DNA双参数流式细胞术分别分析了增殖和细胞周期动力学。结果：电离辐射导致HMC-1细胞释放5-羟色胺。在IPC-298细胞上检测到血清素受体的表达。血清素增强了辐射诱导的黑色素瘤细胞增殖的减少。 5-羟色胺和电离辐射可协同增加黑色素瘤细胞上黏附分子的表达，并改善细胞对纤连蛋白的黏附。细胞粘附分子表达的上调被磷脂酰肌醇3-激酶，有丝分裂原激活的蛋白（MAP）ERK激酶和蛋白激酶C的抑制剂所减弱。人黑色素瘤细胞。我们假设辐射诱导的肥大细胞脱粒和介质释放对恶性黑色素瘤细胞的发展有很大的影响。

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