Downregulation of DLL4 predicts poor survival in non-small cell lung cancer patients due to promotion of lymph node metastasis

被引：4

作者：

Liu, Hongzhou ^{[1
,6
]}

Peng, Jie ^{[2
]}

Zhao, Meizhen ^{[3
]}

Ma, Pei ^{[1
]}

Zhong, Jun ^{[4
]}

Li, Shuang ^{[5
]}

Lu, Zhongxin ^{[1
,6
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Cent Hosp Wuhan, Dept Med Lab, Wuhan 430014, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan Med & Healthcare Ctr Women & Children, Dept Stomatol, Wuhan 430015, Hubei, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Wuhan 430030, Hubei, Peoples R China

[4] Wuhan Univ, Zhongnan Hosp, Dept Oncol Surg 2, Wuhan 430071, Hubei, Peoples R China

[5] Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan Med & Healthcare Ctr Women & Children, Dept Urol Surg, Wuhan 430015, Hubei, Peoples R China

[6] Huazhong Univ Sci & Technol, Tongji Med Coll, Cent Hosp Wuhan, Key Lab Mol Diag Hubei Prov, Wuhan 430014, Hubei, Peoples R China

来源：

ONCOLOGY REPORTS | 2018年 / 40卷 / 05期

关键词：

non-small cell lung cancer; DLL4; proliferation; metastasis; INHIBITS TUMOR-GROWTH; UP-REGULATION; EXPRESSION; BEHAVIOR; ADENOCARCINOMA; PROLIFERATION; ANGIOGENESIS;

D O I：

10.3892/or.2018.6679

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Delta-like 4 (DLL4) is a membrane-bound ligand, which belongs to the Notch signaling pathway and plays important roles in angiogenesis and vascular development. The expression of DLL4 in non-small cell lung cancer (NSCLC) remains unclear. Therefore, DLL4 expression was detected in clinical specimens using quantum dots (QDs)-immunohistochemistry (IHC) and lung cancer cell lines by quantitative real-time polymerase chain reaction. The protein levels of DLL4 were decreased in the tumor tissues of NSCLC patients and lung cancer cell lines. Kaplan-Meier analysis indicated that low expression of DLL4 predicted poor survival rate of NSCLC patients. A549 and A427 cells transfected with pCMV-DLL4 exhibited reduced cell proliferation, migration and invasion using MTT assay, wound healing assay and Transwell assay. These data indicate that DLL4 represents a new prognostic biomarker for NSCLC, and DLL4 overexpression inhibits cell proliferation and metastasis in vitro.

引用

页码：2988 / 2996

页数：9

共 32 条

[1] miR-27b controls venous specification and tip cell fate [J].

Biyashev, Dauren ;

Veliceasa, Dorina ;

Topczewski, Jacek ;

Topczewska, Jolanta M. ;

Mizgirev, Igor ;

Vinokour, Elena ;

Reddi, Alagarsamy L. ;

Licht, Jonathan D. ;

Revskoy, Sergei Y. ;

Volpert, Olga V. .

BLOOD, 2012, 119 (11) :2679-2687

[2] The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis [J].

Bridge, Gemma ;

Monteiro, Rui ;

Henderson, Stephen ;

Emuss, Victoria ;

Lagos, Dimitris ;

Georgopoulou, Dimitra ;

Patient, Roger ;

Boshoff, Chris .

BLOOD, 2012, 120 (25) :5063-5072

[3] microRNA-99a is downregulated and promotes proliferation, migration and invasion in non-small cell lung cancer A549 and H1299 cells [J].

Chen, Changjin ;

Zhao, Ziyi ;

Liu, Yu ;

Mu, Dezhi .

ONCOLOGY LETTERS, 2015, 9 (03) :1128-1134

[4] Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development [J].

Gale, NW ;

Dominguez, MG ;

Noguera, I ;

Pan, L ;

Hughes, V ;

Valenzuela, DM ;

Murphy, AJ ;

Adams, NC ;

Lin, HC ;

Holash, J ;

Thurston, G ;

Yancopoulos, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (45) :15949-15954

[5] Established, emerging and elusive molecular targets in the treatment of lung cancer [J].

Gallant, Jean-Nicolas ;

Lovly, Christine M. .

JOURNAL OF PATHOLOGY, 2018, 244 (05) :565-577

[6] Beyond EGFR and ALK: targeting rare mutations in advanced non-small cell lung cancer [J].

Gkolfinopoulos, Stavros ;

Mountzios, Giannis .

ANNALS OF TRANSLATIONAL MEDICINE, 2018, 6 (08)

[7] NOTCH SIGNALING IN THE VASCULATURE [J].

Gridley, Thomas .

NOTCH SIGNALING, 2010, 92 :277-309

[8] Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma [J].

Haller, B. K. ;

Brave, A. ;

Wallgard, E. ;

Roswall, P. ;

Sunkari, V. G. ;

Mattson, U. ;

Hallengard, D. ;

Catrina, S-B ;

Hellstrom, M. ;

Pietras, K. .

ONCOGENE, 2010, 29 (30) :4276-4286

[9] Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis [J].

Hellstroem, Mats ;

Phng, Li-Kun ;

Hofmann, Jennifer J. ;

Wallgard, Elisabet ;

Coultas, Leigh ;

Lindblom, Per ;

Alva, Jackelyn ;

Nilsson, Ann-Katrin ;

Karlsson, Linda ;

Gaiano, Nicholas ;

Yoon, Keejung ;

Rossant, Janet ;

Iruela-Arispe, M. Luisa ;

Kalen, Mattias ;

Gerhardt, Holger ;

Betsholtz, Christer .

NATURE, 2007, 445 (7129) :776-780

[10] Expression of Vascular Notch Ligand Delta-Like 4 and Inflammatory Markers in Breast Cancer [J].

Jubb, Adrian M. ;

Soilleux, Elizabeth J. ;

Turley, Helen ;

Steers, Graham ;

Parker, Andrew ;

Low, Irene ;

Blades, Jennifer ;

Li, Ji-Liang ;

Allen, Paul ;

Leek, Russell ;

Noguera-Troise, Irene ;

Gatter, Kevin C. ;

Thurston, Gavin ;

Harris, Adrian L. .

AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (04) :2019-2028

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