title: Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis.
abstract: OBJECTIVE
  Uveal melanoma (UM) is the most common primary intraocular tumor in adults and the presence of infiltrating leucocytes is associated with a poor prognosis. Little is known how infiltrating leucocytes influence the tumor cells. The purpose of this study was to investigate the effect of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes.
  
  
  METHODS
  We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma gene expression was quantified using a microarray. Protein expression in the supernatant was quantified with ELISA or cytometric bead array. For the monocyte migration assay, a transwell plate was used.
  
  
  RESULTS
  Gene-expression analysis of UM cell lines showed that coculture with activated T cells resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines coincided with an increased chemotactic capacity of the supernatant toward monocytes.
  
  
  CONCLUSIONS
  Cytokines derived from activated T cells shifted the UM cell transcriptome toward a more inflammatory state, including upregulation of several chemokines, which led to an increased migration of monocytes. Therefore, UM cells might actively participate in generating a tumor-promoting inflammatory microenvironment.
authors: Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, Denmark.
authors: Tina
authors: T
authors: Jehs
authors: Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, Denmark.
authors: Carsten
authors: C
authors: Faber
authors: Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, Denmark.
authors: Helene B
authors: HB
authors: Juel
authors: Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Inge H G
authors: IH
authors: Bronkhorst
authors: Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Martine J
authors: MJ
authors: Jager
authors: Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, Denmark.
authors: Mogens H
authors: MH
authors: Nissen
mesh_terms: D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism*; D046228:Microarray Analysis; D009000:Monocytes / Q000502:physiology*; D014604:Uveal Neoplasms / Q000378:metabolism*; D000098943:Uveal Melanoma
chemical_list: D018925:Chemokines
keywords: chemokines; inflammation; monocyte migration; uveal melanoma