Cargando…

Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer

The tyrosine kinase receptor EphB4 and its ligand ephrin-B2 interact through cell-to-cell contacts. Upon interaction, EphB4 transmits bidirectional signals. A forward signal inside EphB4-expressing cells is believed to suppress tumor growth, while inside the ephrin-expressing cells, an oncogenic rev...

Descripción completa

Detalles Bibliográficos
Autores principales: Magic, Zeljana, Sandström, Josefine, Perez-Tenorio, Gizeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831205/
https://www.ncbi.nlm.nih.gov/pubmed/31638179
http://dx.doi.org/10.3892/ijo.2019.4892
_version_ 1783465915198734336
author Magic, Zeljana
Sandström, Josefine
Perez-Tenorio, Gizeh
author_facet Magic, Zeljana
Sandström, Josefine
Perez-Tenorio, Gizeh
author_sort Magic, Zeljana
collection PubMed
description The tyrosine kinase receptor EphB4 and its ligand ephrin-B2 interact through cell-to-cell contacts. Upon interaction, EphB4 transmits bidirectional signals. A forward signal inside EphB4-expressing cells is believed to suppress tumor growth, while inside the ephrin-expressing cells, an oncogenic reverse signal arises. In breast cancer cells with a high EphB4 receptor expression the forward signal is low, in part due to the low expression of the ligand ephrin-B2. Therefore, we hypothesized that by re-introducing the ligand in EphB4-positive cells, tumor suppression could be induced by the stimulation of the forward signal. This question was addressed in vitro by the stable lentiviral infection of breast cancer cells with either wild-type EFNB2 or with a mutant EFNB2-5F, unable to transmit reverse signaling. Furthermore, we investigated ephrin-B and EphB4 protein expression in 216 paraffin-embedded tumors using immunohistochemistry. The in vitro results indicated that ephrin-B2 expression was associated with a lower cell proliferation, migration and motility compared with the control cells. These effects were more pronounced when the cells lacked the ability to transmit the reverse signal (B2-5F). In clinical material, ephrin-B protein expression was associated with a positive estrogen receptor (ER) status, a low HER-2 expression and was negatively associated with Nottingham histologic grade (NHG) III. Ephrin-B expression indicated a good prognosis, whereas EphB4 expression was associated with a shorter metastasis-free survival in univariate and multivariate analysis. Furthermore, the prognostic value of EFNB2 and EPHB4 was confirmed at the gene expression level in public datasets. Thus, on the whole, the findings of this study suggest that ephrin-B2 expression is associated with less proliferation and lower motility of breast cancer cells and with a longer patient survival in breast cancer.
format Online
Article
Text
id pubmed-6831205
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-68312052019-11-07 Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer Magic, Zeljana Sandström, Josefine Perez-Tenorio, Gizeh Int J Oncol Articles The tyrosine kinase receptor EphB4 and its ligand ephrin-B2 interact through cell-to-cell contacts. Upon interaction, EphB4 transmits bidirectional signals. A forward signal inside EphB4-expressing cells is believed to suppress tumor growth, while inside the ephrin-expressing cells, an oncogenic reverse signal arises. In breast cancer cells with a high EphB4 receptor expression the forward signal is low, in part due to the low expression of the ligand ephrin-B2. Therefore, we hypothesized that by re-introducing the ligand in EphB4-positive cells, tumor suppression could be induced by the stimulation of the forward signal. This question was addressed in vitro by the stable lentiviral infection of breast cancer cells with either wild-type EFNB2 or with a mutant EFNB2-5F, unable to transmit reverse signaling. Furthermore, we investigated ephrin-B and EphB4 protein expression in 216 paraffin-embedded tumors using immunohistochemistry. The in vitro results indicated that ephrin-B2 expression was associated with a lower cell proliferation, migration and motility compared with the control cells. These effects were more pronounced when the cells lacked the ability to transmit the reverse signal (B2-5F). In clinical material, ephrin-B protein expression was associated with a positive estrogen receptor (ER) status, a low HER-2 expression and was negatively associated with Nottingham histologic grade (NHG) III. Ephrin-B expression indicated a good prognosis, whereas EphB4 expression was associated with a shorter metastasis-free survival in univariate and multivariate analysis. Furthermore, the prognostic value of EFNB2 and EPHB4 was confirmed at the gene expression level in public datasets. Thus, on the whole, the findings of this study suggest that ephrin-B2 expression is associated with less proliferation and lower motility of breast cancer cells and with a longer patient survival in breast cancer. D.A. Spandidos 2019-10-04 /pmc/articles/PMC6831205/ /pubmed/31638179 http://dx.doi.org/10.3892/ijo.2019.4892 Text en Copyright: © Magic et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Magic, Zeljana
Sandström, Josefine
Perez-Tenorio, Gizeh
Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
title Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
title_full Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
title_fullStr Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
title_full_unstemmed Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
title_short Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
title_sort ephrin-b2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831205/
https://www.ncbi.nlm.nih.gov/pubmed/31638179
http://dx.doi.org/10.3892/ijo.2019.4892
work_keys_str_mv AT magiczeljana ephrinb2inhibitscellproliferationandmotilityinvitroandpredictslongermetastasisfreesurvivalinbreastcancer
AT sandstromjosefine ephrinb2inhibitscellproliferationandmotilityinvitroandpredictslongermetastasisfreesurvivalinbreastcancer
AT pereztenoriogizeh ephrinb2inhibitscellproliferationandmotilityinvitroandpredictslongermetastasisfreesurvivalinbreastcancer