Elevated PLGF contributes to small-cell lung cancer brain metastasis

被引：79

作者：

Li, B. ^{[1
,2
]}

Wang, C. ^{[1
,2
,3
]}

Zhang, Y. ^{[1
,2
]}

Zhao, X. Y. ^{[1
,2
,4
]}

Huang, B. ^{[5
]}

Wu, P. F. ^{[6
]}

Li, Q. ^{[7
]}

Li, H. ^{[8
]}

Liu, Y. S. ^{[1
,2
]}

Cao, L. Y. ^{[1
,2
]}

Dai, W. M. ^{[1
,2
]}

Fang, W. G. ^{[1
,2
]}

Shang, D. S. ^{[1
,2
]}

Cao, L. ^{[2
,9
]}

Zhao, W. D. ^{[1
,2
]}

Chen, Y. H. ^{[1
,2
]}

机构：

[1] China Med Univ, Dept Dev Biol, Minist Publ Hlth, Key Lab Cell Biol, Shenyang 110001, Peoples R China

[2] China Med Univ, Minist Educ, Key Lab Med Cell Biol, Shenyang 110001, Peoples R China

[3] Liaoning Univ Tradit Chinese Med, Dept Cell Biol, Shenyang, Peoples R China

[4] Shenyang Pharmaceut Univ, Dept Cell Biol, Shenyang, Peoples R China

[5] Liaoning Canc Hosp & Inst, Dept Pathol, Shenyang, Peoples R China

[6] China Med Univ, Hosp 1, Dept Neurosurg, Shenyang 110001, Peoples R China

[7] China Med Univ, Shengjing Hosp, Dept Med Examinat, Shenyang 110001, Peoples R China

[8] China Med Univ, Shengjing Hosp, Dept Geriatr Med, Shenyang 110001, Peoples R China

[9] China Med Univ, Minist Educ, Minist Publ Hlth, Inst Translat Med,Key Lab Cell Biol, Shenyang 110001, Peoples R China

来源：

ONCOGENE | 2013年 / 32卷 / 24期

基金：

中国国家自然科学基金;

关键词：

blood-brain barrier; brain metastasis; PLGF; Rho kinase; small-cell lung cancer; ENDOTHELIAL GROWTH-FACTOR; TIGHT JUNCTION PROTEINS; BREAST-CANCER; VASCULAR-PERMEABILITY; DIABETIC-RETINOPATHY; KINASE; OCCLUDIN; BARRIER; PHOSPHORYLATION; ACTIVATION;

D O I：

10.1038/onc.2012.313

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Brain metastasis (BM) is a major cause of mortality in small-cell lung cancer (SCLC) patients; however, the molecular pathway of SCLC BM remains largely unknown because of a lack of investigation. Here we screen the levels of some candidate-soluble factors in the serum of SCLC patients and find that SCLC patients with high levels of placental growth factor (PLGF) are prone to BM. Using in vitro blood-brain barrier model, we show that PLGF derived from SCLC cells triggers vascular endothelial growth factor receptor1- Rho-extracellular regulated protein kinase 1/2 signaling axis activation, results in disassembly of tight junction in brain endothelial cells and promotes SCLC cell transendothelial migration. Furthermore, the downregulation of PLGF suppresses SCLC cell metastasis to the brain in an experimental BM model. These data suggest that PLGF is a potential signature of SCLC BM and a prospective therapeutic target for SCLC BM.

引用

页码：2952 / 2962

页数：11

共 47 条

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