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

Autor: Wen-Gang Fang, Shuai Yuan, Tingting Liu, Yu-Hua Chen, Jiusheng Jiang, Ziwei Miao, Bo Li
Rok vydání: 2015
Předmět:
transendothelial migration
Lung Neoplasms
Nicotinamide phosphoribosyltransferase
Metastasis
lcsh:Chemistry
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
brain metastasis
CC chemokine ligand 2 (CCL2)
Neoplasm Metastasis
Nicotinamide Phosphoribosyltransferase
lcsh:QH301-705.5
Spectroscopy
Chemokine CCL2
SCLC
General Medicine
blood–brain barrier (BBB)
Computer Science Applications
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Blood-Brain Barrier
Signal Transduction
medicine.medical_specialty
Biology
CCL2
Blood–brain barrier
Catalysis
Article
Inorganic Chemistry
Downregulation and upregulation
Internal medicine
Cell Line
Tumor
visfatin
medicine
Humans
RNA
Messenger
Physical and Theoretical Chemistry
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Organic Chemistry
Transendothelial and Transepithelial Migration
medicine.disease
Small Cell Lung Carcinoma
respiratory tract diseases
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
Proto-Oncogene Proteins c-akt
Brain metastasis
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 16, Iss 5, Pp 11439-11451 (2015)
Volume 16
Issue 5
Pages 11439-11451
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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