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Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model

Standard

Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model. / Broggini, Thomas; Piffko, Andras; Hoffmann, Christian J; Ghori, Adnan; Harms, Christoph; Adams, Ralf H; Vajkoczy, Peter; Czabanka, Marcus.

In: ONCOGENE, Vol. 39, No. 47, 11.2020, p. 7063-7075.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Broggini, T, Piffko, A, Hoffmann, CJ, Ghori, A, Harms, C, Adams, RH, Vajkoczy, P & Czabanka, M 2020, 'Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model', ONCOGENE, vol. 39, no. 47, pp. 7063-7075. https://doi.org/10.1038/s41388-020-01473-y

APA

Broggini, T., Piffko, A., Hoffmann, C. J., Ghori, A., Harms, C., Adams, R. H., Vajkoczy, P., & Czabanka, M. (2020). Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model. ONCOGENE, 39(47), 7063-7075. https://doi.org/10.1038/s41388-020-01473-y

Vancouver

Broggini T, Piffko A, Hoffmann CJ, Ghori A, Harms C, Adams RH et al. Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model. ONCOGENE. 2020 Nov;39(47):7063-7075. https://doi.org/10.1038/s41388-020-01473-y

Bibtex

@article{8606a6d4e7d142219ae4baa14bac4b19,
title = "Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model",
abstract = "Metastases account for the majority of cancer deaths. Bone represents one of the most common sites of distant metastases, and spinal bone metastasis is the most common source of neurological morbidity in cancer patients. During metastatic seeding of cancer cells, endothelial-tumor cell interactions govern extravasation to the bone and potentially represent one of the first points of action for antimetastatic treatment. The ephrin-B2-EphB4 pathway controls cellular interactions by inducing repulsive or adhesive properties, depending on forward or reverse signaling. Here, we report that in an in vivo metastatic melanoma model, ephrin-B2-mediated activation of EphB4 induces tumor cell repulsion from bone endothelium, translating in reduced spinal bone metastatic loci and improved neurological function. Selective ephrin-B2 depletion in endothelial cells or EphB4 inhibition increases bone metastasis and shortens the time window to hind-limb locomotion deficit from spinal cord compression. EphB4 overexpression in melanoma cells ameliorates the metastatic phenotype and improves neurological outcome. Timely harvesting of bone tissue after tumor cell injection and intravital bone microscopy revealed less tumor cells attached to ephrin-B2-positive endothelial cells. These results suggest that ephrin-B2-EphB4 communication influences bone metastasis formation by altering melanoma cell repulsion/adhesion to bone endothelial cells, and represents a molecular target for therapeutic intervention.",
keywords = "Animals, Bone Marrow/diagnostic imaging, Cell Adhesion, Cell Communication/drug effects, Cell Line, Tumor/transplantation, Endothelial Cells/pathology, Female, Intravital Microscopy, Magnetic Resonance Imaging, Male, Melanoma, Experimental/drug therapy, Mice, Mice, Knockout, Microscopy, Video, Osteoblasts/pathology, Pyrazoles/pharmacology, Pyrimidines/pharmacology, Receptor, EphB2/genetics, Receptor, EphB4/antagonists & inhibitors, Skin Neoplasms/drug therapy, Skull/pathology, Spinal Cord Compression/diagnosis, Spinal Neoplasms/complications, Spine/cytology",
author = "Thomas Broggini and Andras Piffko and Hoffmann, {Christian J} and Adnan Ghori and Christoph Harms and Adams, {Ralf H} and Peter Vajkoczy and Marcus Czabanka",
year = "2020",
month = nov,
doi = "10.1038/s41388-020-01473-y",
language = "English",
volume = "39",
pages = "7063--7075",
journal = "ONCOGENE",
issn = "0950-9232",
publisher = "NATURE PUBLISHING GROUP",
number = "47",

}

RIS

TY - JOUR

T1 - Ephrin-B2-EphB4 communication mediates tumor-endothelial cell interactions during hematogenous spread to spinal bone in a melanoma metastasis model

AU - Broggini, Thomas

AU - Piffko, Andras

AU - Hoffmann, Christian J

AU - Ghori, Adnan

AU - Harms, Christoph

AU - Adams, Ralf H

AU - Vajkoczy, Peter

AU - Czabanka, Marcus

PY - 2020/11

Y1 - 2020/11

N2 - Metastases account for the majority of cancer deaths. Bone represents one of the most common sites of distant metastases, and spinal bone metastasis is the most common source of neurological morbidity in cancer patients. During metastatic seeding of cancer cells, endothelial-tumor cell interactions govern extravasation to the bone and potentially represent one of the first points of action for antimetastatic treatment. The ephrin-B2-EphB4 pathway controls cellular interactions by inducing repulsive or adhesive properties, depending on forward or reverse signaling. Here, we report that in an in vivo metastatic melanoma model, ephrin-B2-mediated activation of EphB4 induces tumor cell repulsion from bone endothelium, translating in reduced spinal bone metastatic loci and improved neurological function. Selective ephrin-B2 depletion in endothelial cells or EphB4 inhibition increases bone metastasis and shortens the time window to hind-limb locomotion deficit from spinal cord compression. EphB4 overexpression in melanoma cells ameliorates the metastatic phenotype and improves neurological outcome. Timely harvesting of bone tissue after tumor cell injection and intravital bone microscopy revealed less tumor cells attached to ephrin-B2-positive endothelial cells. These results suggest that ephrin-B2-EphB4 communication influences bone metastasis formation by altering melanoma cell repulsion/adhesion to bone endothelial cells, and represents a molecular target for therapeutic intervention.

AB - Metastases account for the majority of cancer deaths. Bone represents one of the most common sites of distant metastases, and spinal bone metastasis is the most common source of neurological morbidity in cancer patients. During metastatic seeding of cancer cells, endothelial-tumor cell interactions govern extravasation to the bone and potentially represent one of the first points of action for antimetastatic treatment. The ephrin-B2-EphB4 pathway controls cellular interactions by inducing repulsive or adhesive properties, depending on forward or reverse signaling. Here, we report that in an in vivo metastatic melanoma model, ephrin-B2-mediated activation of EphB4 induces tumor cell repulsion from bone endothelium, translating in reduced spinal bone metastatic loci and improved neurological function. Selective ephrin-B2 depletion in endothelial cells or EphB4 inhibition increases bone metastasis and shortens the time window to hind-limb locomotion deficit from spinal cord compression. EphB4 overexpression in melanoma cells ameliorates the metastatic phenotype and improves neurological outcome. Timely harvesting of bone tissue after tumor cell injection and intravital bone microscopy revealed less tumor cells attached to ephrin-B2-positive endothelial cells. These results suggest that ephrin-B2-EphB4 communication influences bone metastasis formation by altering melanoma cell repulsion/adhesion to bone endothelial cells, and represents a molecular target for therapeutic intervention.

KW - Animals

KW - Bone Marrow/diagnostic imaging

KW - Cell Adhesion

KW - Cell Communication/drug effects

KW - Cell Line, Tumor/transplantation

KW - Endothelial Cells/pathology

KW - Female

KW - Intravital Microscopy

KW - Magnetic Resonance Imaging

KW - Male

KW - Melanoma, Experimental/drug therapy

KW - Mice

KW - Mice, Knockout

KW - Microscopy, Video

KW - Osteoblasts/pathology

KW - Pyrazoles/pharmacology

KW - Pyrimidines/pharmacology

KW - Receptor, EphB2/genetics

KW - Receptor, EphB4/antagonists & inhibitors

KW - Skin Neoplasms/drug therapy

KW - Skull/pathology

KW - Spinal Cord Compression/diagnosis

KW - Spinal Neoplasms/complications

KW - Spine/cytology

U2 - 10.1038/s41388-020-01473-y

DO - 10.1038/s41388-020-01473-y

M3 - SCORING: Journal article

C2 - 32989254

VL - 39

SP - 7063

EP - 7075

JO - ONCOGENE

JF - ONCOGENE

SN - 0950-9232

IS - 47

ER -