title: ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome.
abstract: BACKGROUND
  Clinical treatment of spinal metastasis is gaining in complexity while the underlying biology remains unknown. Insufficient biological understanding is due to a lack of suitable experimental animal models. Intercellular adhesion molecule-1 (ICAM1) has been implicated in metastasis formation. Its role in spinal metastasis remains unclear. It was the aim to generate a reliable spinal metastasis model in mice and to investigate metastasis formation under ICAM1 depletion.
  
  
  METHODS
  B16 melanoma cells were infected with a lentivirus containing firefly luciferase (B16-luc). Stable cell clones (B16-luc) were injected retrogradely into the distal aortic arch. Spinal metastasis formation was monitored using in vivo bioluminescence imaging/MRI. Neurological deficits were monitored daily. In vivo selected, metastasized tumor cells were isolated (mB16-luc) and reinjected intraarterially. mB16-luc cells were injected intraarterially in ICAM1 KO mice. Metastasis distribution was analyzed using organ-specific fluorescence analysis.
  
  
  RESULTS
  Intraarterial injection of B16-luc and metastatic mB16-luc reliably induced spinal metastasis formation with neurological deficits (B16-luc:26.5, mB16-luc:21 days, p<0.05). In vivo selection increased the metastatic aggressiveness and led to a bone specific homing phenotype. Thus, mB16-luc cells demonstrated higher number (B16-luc: 1.2±0.447, mB16-luc:3.2±1.643) and increased total metastasis volume (B16-luc:2.87±2.453 mm3, mB16-luc:11.19±3.898 mm3, p<0.05) in the spine. ICAM1 depletion leads to a significantly reduced number of spinal metastasis (mB16-luc:1.2±0.84) with improved neurological outcome (29 days). General metastatic burden was significantly reduced under ICAM1 depletion (control: 3.47×10(7)±1.66×10(7); ICAM-1-/-: 5.20×10(4)±4.44×10(4), p<0.05 vs. control)
  
  
  CONCLUSIONS
  Applying a reliable animal model for spinal metastasis, ICAM1 depletion reduces spinal metastasis formation due to an organ-unspecific reduction of metastasis development.
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Charite, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Broggini
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Charite, Augustenburger Platz 1, 13353, Berlin, Germany. marcus.czabanka@charite.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Czabanka
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Charite, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Andras
authors.initials: A
authors.lastname: Piffko
authors.affiliation: Department of Experimental Neurology, Universitätsmedizin Charite, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Harms
authors.affiliation: Department of Experimental Neurology, Universitätsmedizin Charite, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoffmann
authors.affiliation: Experimental Nephrology, Universitätsklinikum, Jena, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Mrowka
authors.affiliation: Experimental Nephrology, Universitätsklinikum, Jena, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Wenke
authors.affiliation: Theodor Kocher Institute, University of Berne, Berne, Germany.
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.affiliation: Department for Hepatology and Gastroenterology, Charite, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Grötzinger
authors.affiliation: Department of Neurosurgery, Universitätsmedizin Charite, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005822:Genetic Vectors; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008546:Melanoma, Experimental / Q000150:complications / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D018345:Mice, Knockout; D013117:Spinal Cord Compression / Q000209:etiology; D013125:Spinal Neoplasms / Q000150:complications / Q000517:prevention & control / Q000556:secondary*
chemical_list: D018799:Intercellular Adhesion Molecule-1
keywords: B16; Experimental spinal metastasis; ICAM-1; Spinal compression