ORIGINAL ARTICLE ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome Thomas Broggini • Marcus Czabanka • Andras Piffko • Christoph Harms • Christian Hoffmann • Ralf Mrowka • Frank Wenke • Urban Deutsch • Carsten Gro ¨tzinger • Peter Vajkoczy Received: 24 October 2014 / Revised: 9 February 2015 / Accepted: 11 February 2015 Ó Springer-Verlag Berlin Heidelberg 2015 Abstract Introduction Clinical treatment of spinal metastasis is gaining in complexity while the underlying biology re- mains unknown. Insufficient biological understanding is due to a lack of suitable experimental animal models. In- tercellular adhesion molecule-1 (ICAM1) has been impli- cated 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. Material and 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 mon- itored using in vivo bioluminescence imaging/MRI. Neuro- logical deficits were monitored daily. In vivo selected, metastasized tumor cells were isolated (mB16-luc) and reinjected intraarterially. mB16-luc cells were injected in- traarterially 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 ag- gressiveness 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 mm 3 , mB16- luc:11.19 ± 3.898 mm 3 , 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 neuro- logical outcome (29 days). General metastatic burden was significantly reduced under ICAM1 depletion (control: 3.47 9 10 7 ± 1.66 9 10 7 ; ICAM-1 -/- : 5.20 9 10 4 ± 4.44 9 10 4 , p \ 0.05 vs. control) Conclusion Applying a reliable animal model for spinal metastasis, ICAM1 depletion reduces spinal metastasis formation due to an organ-unspecific reduction of metas- tasis development. Keywords Experimental spinal metastasis Á ICAM-1 Á B16 Á Spinal compression Introduction Improved diagnostics and oncological therapies are caus- ing an increased incidence of spinal metastasis. Currently, 70 % of all oncological patients develop spinal metastasis and 10 % of these patients experience neurological deficits due to epidural myelon compression [1–3]. Therefore, an increasing number of complex surgical therapies have to be T. Broggini and M. Czabanka contributed equally to this work. T. Broggini Á M. Czabanka (&) Á A. Piffko Á P. Vajkoczy Department of Neurosurgery, Universita ¨tsmedizin Charite, Augustenburger Platz 1, 13353 Berlin, Germany e-mail: marcus.czabanka@charite.de C. Harms Á C. Hoffmann Department of Experimental Neurology, Universita ¨tsmedizin Charite, Berlin, Germany R. Mrowka Á F. Wenke Experimental Nephrology, Universita ¨tsklinikum, Jena, Germany U. Deutsch Theodor Kocher Institute, University of Berne, Berne, Germany C. Gro ¨tzinger Department for Hepatology and Gastroenterology, Charite, Berlin, Germany 123 Eur Spine J DOI 10.1007/s00586-015-3811-7