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01-10-2015 | Original Article

ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome

Authors: Thomas Broggini, Marcus Czabanka, Andras Piffko, Christoph Harms, Christian Hoffmann, Ralf Mrowka, Frank Wenke, Urban Deutsch, Carsten Grötzinger, Peter Vajkoczy

Published in: European Spine Journal | Issue 10/2015

Abstract

Introduction

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.

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 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 × 10⁷ ± 1.66 × 10⁷; ICAM-1 ^−/−: 5.20 × 10⁴ ± 4.44 × 10⁴, 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 metastasis development.

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Title: ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome
Authors: Thomas Broggini
Marcus Czabanka
Andras Piffko
Christoph Harms
Christian Hoffmann
Ralf Mrowka
Frank Wenke
Urban Deutsch
Carsten Grötzinger
Peter Vajkoczy
Publication date: 01-10-2015
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 10/2015
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-015-3811-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome

Abstract

Introduction

Material and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Material and methods

Results

Conclusion

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