title: Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells.
abstract: 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.
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany. kerstin_mueller@hotmail.com
authors.forename: Kerstin
authors.initials: K
authors.lastname: Müller
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Gilbertz
authors.forename: Viktor
authors.initials: V
authors.lastname: Meineke
mesh_terms: D015815:Cell Adhesion Molecules / Q000032:analysis*; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D005260:Female; D006801:Humans; D016023:Integrins / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008407:Mast Cells / Q000502:physiology / Q000528:radiation effects; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D016023:Integrins; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin; D018799:Intercellular Adhesion Molecule-1; D012701:Serotonin