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


Autoria(s): Broggini, Thomas; Czabanka, Marcus; Piffko, Andras; Harms, Christoph; Hoffmann, Christian; Mrowka, Ralf; Wenke, Frank; Deutsch, Urban; Grötzinger, Carsten; Vajkoczy, Peter
Data(s)

01/10/2015

Resumo

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: 3.47×10(7)±1.66×10(7); ICAM-1-/-: 5.20×10(4)±4.44×10(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 metastasis development.

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application/pdf

Identificador

http://boris.unibe.ch/77347/1/art%253A10.1007%252Fs00586-015-3811-7.pdf

Broggini, Thomas; Czabanka, Marcus; Piffko, Andras; Harms, Christoph; Hoffmann, Christian; Mrowka, Ralf; Wenke, Frank; Deutsch, Urban; Grötzinger, Carsten; Vajkoczy, Peter (2015). ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome. European spine journal, 24(10), pp. 2173-2181. Springer 10.1007/s00586-015-3811-7 <http://dx.doi.org/10.1007/s00586-015-3811-7>

doi:10.7892/boris.77347

info:doi:10.1007/s00586-015-3811-7

info:pmid:25711910

urn:issn:0940-6719

Idioma(s)

eng

Publicador

Springer

Relação

http://boris.unibe.ch/77347/

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Broggini, Thomas; Czabanka, Marcus; Piffko, Andras; Harms, Christoph; Hoffmann, Christian; Mrowka, Ralf; Wenke, Frank; Deutsch, Urban; Grötzinger, Carsten; Vajkoczy, Peter (2015). ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome. European spine journal, 24(10), pp. 2173-2181. Springer 10.1007/s00586-015-3811-7 <http://dx.doi.org/10.1007/s00586-015-3811-7>

Palavras-Chave #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed