title: Intravitreally Injected HCmel12 Melanoma Cells Serve as a Mouse Model of Tumor Biology of Intraocular Melanoma.
abstract: OBJECTIVE
  To establish a mouse model with histologic characteristics of uveal melanoma for investigation of intraocular tumor biology of melanoma.
  
  
  METHODS
  After injection of 1 × 10(5) of HCmel12 melanoma cells, a cutaneous melanoma cell line, into the vitreous of CX3CR1(+/GFP) or C57Bl/6 mice (n = 12), tumor growth patterns, clinicopathological features, angiogenesis and metastatic behavior were analyzed by histology (hematoxylin and eosin, periodic acid-Schiff without hematoxylin) and immunohistochemistry (HMB45/MART-1-Ab, F4/80-Ab, green fluorescent protein (GFP)-Ab and VE-cadherin-Ab).
  
  
  RESULTS
  HCmel12 cells formed intraocularly growing tumor masses, which showed histologic features of intraocular melanoma such as angiotropism, intratumoral endothelial-lined vasculature, vasculogenic mimicry including prognostic significant extravascular matrix patterns, and invasion by inflammatory cells, in particular macrophages. There was no difference in tumor growth characteristics between CX3CR1(+/GFP) and C57Bl/6 mice. Five of 10 mice proceeded to extrascleral tumor growth and three of these developed metastases.
  
  
  CONCLUSIONS
  Intraocularly injected HCmel12 cells developed tumor masses with histologic characteristics of aggressive melanoma similar to human uveal melanoma. Since hematogenous dissemination to the liver was not observed, intravitreally injected HCmel12 cells do not qualify as a model for metastasizing intraocular melanoma. However, since the eye represents a semi-closed compartment with access to constant blood supply, these intraocular tumors represent a model for studies of isolated parameters in general tumor biology of intraocular melanoma.
authors: a Department of Ophthalmology , University of Bonn , Bonn , Germany .
authors: Marta M
authors: MM
authors: Kilian
authors: a Department of Ophthalmology , University of Bonn , Bonn , Germany .
authors: Karin U
authors: KU
authors: Loeffler
authors: b Department of Anatomy , University of Veterinary Medicine Hannover , Hannover , Germany , and.
authors: Christiane
authors: C
authors: Pfarrer
authors: a Department of Ophthalmology , University of Bonn , Bonn , Germany .
authors: Frank G
authors: FG
authors: Holz
authors: c Institute of Experimental Immunology, University of Bonn , Bonn , Germany.
authors: Christian
authors: C
authors: Kurts
authors: a Department of Ophthalmology , University of Bonn , Bonn , Germany .
authors: Martina C
authors: MC
authors: Herwig
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D058449:Intravitreal Injections; D058965:MART-1 Antigen / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous; D014604:Uveal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D058951:gp100 Melanoma Antigen; D000098943:Uveal Melanoma; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D015820:Cadherins; D049452:Green Fluorescent Proteins; D058965:MART-1 Antigen; D058950:Melanoma-Specific Antigens; D058951:gp100 Melanoma Antigen; D000099152:Cadherin 5; C548667:MLANA protein, human; C548637:PMEL protein, human; C036763:monocyte-macrophage differentiation antigen
keywords: Animal model; macrophages; metastasis; uveal melanoma; vasculogenic mimicry