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Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2

Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin...

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Detalles Bibliográficos
Autores principales: Liu, Tingting, Miao, Ziwei, Jiang, Jiusheng, Yuan, Shuai, Fang, Wengang, Li, Bo, Chen, Yuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463709/
https://www.ncbi.nlm.nih.gov/pubmed/25993304
http://dx.doi.org/10.3390/ijms160511439
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author Liu, Tingting
Miao, Ziwei
Jiang, Jiusheng
Yuan, Shuai
Fang, Wengang
Li, Bo
Chen, Yuhua
author_facet Liu, Tingting
Miao, Ziwei
Jiang, Jiusheng
Yuan, Shuai
Fang, Wengang
Li, Bo
Chen, Yuhua
author_sort Liu, Tingting
collection PubMed
description Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin has been considered as a novel pro-inflammatory adipocytokine involved in various cancers. Herein, we present evidence that elevated levels of visfatin in the serum of SCLC patients were associated with brain metastasis, and visfain was increased in NCI-H446 cells, a SCLC cell line, during interacting with human brain microvascular endothelial cells (HBMEC). Using in vitro BBB model, we found that visfatin could promote NCI-H446 cells migration across HBMEC monolayer, while the effect was inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC chemokine ligand 2 (CCL2) was involved in visfatin-mediated NCI-H446 cells transendothelial migtation. Results also showed that the upregulation of CCL2 in the co-culture system was reversed by blockade of visfatin. In particular, visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling in NCI-H446 cells. Taken together, we demonstrated that visfatin was a prospective target for SCLC metastasis to brain, and understanding the molecular mediators would lead to effective strategies for inhibition of SCLC brain metastasis.
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spelling pubmed-44637092015-06-16 Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2 Liu, Tingting Miao, Ziwei Jiang, Jiusheng Yuan, Shuai Fang, Wengang Li, Bo Chen, Yuhua Int J Mol Sci Article Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin has been considered as a novel pro-inflammatory adipocytokine involved in various cancers. Herein, we present evidence that elevated levels of visfatin in the serum of SCLC patients were associated with brain metastasis, and visfain was increased in NCI-H446 cells, a SCLC cell line, during interacting with human brain microvascular endothelial cells (HBMEC). Using in vitro BBB model, we found that visfatin could promote NCI-H446 cells migration across HBMEC monolayer, while the effect was inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC chemokine ligand 2 (CCL2) was involved in visfatin-mediated NCI-H446 cells transendothelial migtation. Results also showed that the upregulation of CCL2 in the co-culture system was reversed by blockade of visfatin. In particular, visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling in NCI-H446 cells. Taken together, we demonstrated that visfatin was a prospective target for SCLC metastasis to brain, and understanding the molecular mediators would lead to effective strategies for inhibition of SCLC brain metastasis. MDPI 2015-05-18 /pmc/articles/PMC4463709/ /pubmed/25993304 http://dx.doi.org/10.3390/ijms160511439 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Tingting
Miao, Ziwei
Jiang, Jiusheng
Yuan, Shuai
Fang, Wengang
Li, Bo
Chen, Yuhua
Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
title Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
title_full Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
title_fullStr Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
title_full_unstemmed Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
title_short Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
title_sort visfatin mediates sclc cells migration across brain endothelial cells through upregulation of ccl2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463709/
https://www.ncbi.nlm.nih.gov/pubmed/25993304
http://dx.doi.org/10.3390/ijms160511439
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