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.
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 humanmelanoma 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 humanmelanoma cells. We postulate that radiation-induced mast cell degranulation and mediator release have a great impact on malignant melanoma cell development.
Authors: Marloes A M Peters; Coby Meijer; Rudolf S N Fehrmann; Annemiek M E Walenkamp; Ido P Kema; Elisabeth G E de Vries; Harry Hollema; Sjoukje F Oosting Journal: Pathol Oncol Res Date: 2019-09-02 Impact factor: 3.201