TY  - JOUR
A1  - Piffkó, András
A1  - Broggini, Thomas
A1  - Harms, Christoph
A1  - Adams, Ralf Heinrich
A1  - Vajkoczy, Peter
A1  - Czabanka, Marcus Alexander
T1  - Ligand-dependent and ligand-independent effects of Ephrin-B2-EphB4 signaling in melanoma metastatic spine disease
T2  - International journal of molecular sciences
N2  - Tumor–endothelial cell interactions represent an essential mechanism in spinal metastasis. Ephrin-B2–EphB4 communication induces tumor cell repulsion from the endothelium in metastatic melanoma, reducing spinal bone metastasis formation. To shed further light on the Ephrin-B2–EphB4 signaling mechanism, we researched the effects of pharmacological EphB4 receptor stimulation and inhibition in a ligand-dependent/independent context. We chose a preventative and a post-diagnostic therapeutic window. EphB4 stimulation during tumor cell seeding led to an increase in spinal metastatic loci and number of disseminated melanoma cells, as well as earlier locomotion deficits in the presence of endothelial Ephrin-B2. In the absence of endothelial Ephrin-B2, reduction of metastatic loci with a later manifestation of locomotion deficits occurred. Thus, EphB4 receptor stimulation affects metastatic dissemination depending on the presence/absence of endothelial Ephrin-B2. After the manifestation of solid metastasis, EphB4 kinase inhibition resulted in significantly earlier manifestation of locomotion deficits in the presence of the ligand. No post-diagnostic treatment effect was found in the absence of endothelial Ephrin-B2. For solid metastasis treatment, EphB4 kinase inhibition induced prometastatic effects in the presence of endothelial Ephrin-B2. In the absence of endothelial Ephrin-B2, both therapies showed no effect on the growth of solid metastasis.
KW  - spinal bone metastasis
KW  - cancer therapy
KW  - seed and soil
KW  - Ephrin-B2–EphB4
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62195
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621954
SN  - 1422-0067
N1  - This research was funded by the German research foundation DFG GEPRIS: 267716524 and the FOR2325 DFG Forschergruppe. A.P. received a Berlin Institute of Health (BIH) scholarship for this project. T.B. was a doctoral student of the Charité Medical Neuroscience, NeuroCure cluster of excellence graduate school, received the Ernst von Leyden fellowship from the ‘Berliner Krebsgesellschaft e.V.’ and the Early/Advanced Postdoc Mobility fellowship from the Swiss National Science Foundation. M.C. was part of the Friedrich C. Luft Clinical Scientist Pilot Program funded by the Volkswagen Foundation and the Charité Foundation.
VL  - 22.2021
IS  - 15, art. 8028
SP  - 1
EP  - 13
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -