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

International Journal of Molecular Sciences

Tingting Liu²  Ziwei Miao²  Jiusheng Jiang²  Shuai Yuan²  Wengang Fang²  Bo Li²  Yuhua Chen¹ 

[1] Key Lab of Cell Biology, Ministry of Public Health, Key Lab of Medical Cell Biology, Ministry of Education, Department of Developmental Biology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;

关键词: brain metastasis;    SCLC;    visfatin;    transendothelial migration;    blood–brain barrier (BBB);    CC chemokine ligand 2 (CCL2);   

DOI  :  10.3390/ijms160511439

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.