Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

被引：38

作者：

Chiang, Kun-Chun ^{[1
,2
]}

Yeh, Ta-Sen ^{[3
,4
]}

Wu, Ren-Chin ^{[4
,5
]}

Pang, Jong-Hwei S. ^{[6
]}

Cheng, Chi-Tung ^{[3
,4
]}

Wang, Shang-Yu ^{[3
,4
]}

Juang, Horng-Heng ^{[7
,8
]}

Yeh, Chun-Nan ^{[3
,4
]}

机构：

[1] Chang Gung Univ, Chang Gung Mem Hosp, Dept Gen Surg, Keelung, Taiwan

[2] Keelung Chang Gung Mem Hosp, Zebrafish Ctr, Keelung, Taiwan

[3] Chang Gung Univ, Chang Gung Mem Hosp, Gen Surg Dept, Taoyuan, Taiwan

[4] Chang Gung Univ, Chang Gung Mem Hosp, Liver Res Ctr, Taoyuan, Taiwan

[5] Chang Gung Univ, Chang Gung Mem Hosp, Dept Pathol, Taoyuan, Taiwan

[6] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan, Taiwan

[7] Chang Gung Univ, Dept Anat, Coll Med, Taoyuan 333, Taiwan

[8] Chang Gung Mem Hosp, Dept Urol, Tao Yuan, Taiwan

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

GELATINASE-ASSOCIATED LIPOCALIN; MATRIX METALLOPROTEINASES; SIGNALING PATHWAY; GASTRIC-CANCER; CELL-GROWTH; VITAMIN-D; GENE; NGAL; EXPRESSION; ROLES;

D O I：

10.1038/srep36138

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA.

引用

页数：10

共 53 条

[1] CDH3/P-Cadherin regulates migration of HuCCT1 cholangiocarcinoma cells [J].

Baek, Sungmin ;

Lee, Yong-Whan ;

Yoon, Sik ;

Baek, Sun-Yong ;

Kim, Bong-Seon ;

Oh, Sae-Ock .

ANATOMY & CELL BIOLOGY, 2010, 43 (02) :110-117

[2]

Bandyopadhyay S, 2003, CANCER RES, V63, P1731

[3] Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer [J].

Bauer, Maret ;

Eickhoff, Jens C. ;

Gould, Michael N. ;

Mundhenke, Christoph ;

Maass, Nicolai ;

Friedl, Andreas .

BREAST CANCER RESEARCH AND TREATMENT, 2008, 108 (03) :389-397

[4]

BIRCHMEIER W, 1995, CANCER SURV, V24, P129

[5] Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: A new protein enters the scene [J].

Bolignano, Davide ;

Donato, Valentina ;

Lacquaniti, Antonio ;

Fazio, Maria Rosaria ;

Bono, Caterina ;

Coppolino, Giuseppe ;

Buemi, Michele .

CANCER LETTERS, 2010, 288 (01) :10-16

[6] Diagnostic value of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 pathway in transitional cell carcinoma of the bladder [J].

Candido, Saverio ;

Di Maso, Matteo ;

Serraino, Diego ;

McCubrey, James A. ;

Bortolus, Roberto ;

Zanin, Martina ;

Battiston, Monica ;

Salemi, Rossella ;

Libra, Massimo ;

Polesel, Jerry .

TUMOR BIOLOGY, 2016, 37 (07) :9855-9863

[7] Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy [J].

Candido, Saverio ;

Abrams, Stephen L. ;

Steelman, Linda S. ;

Lertpiriyapong, Kvin ;

Fitzgerald, Timothy L. ;

Martelli, Alberto M. ;

Cocco, Lucio ;

Montalto, Giuseppe ;

Cervello, Melchiorre ;

Polesel, Jerry ;

Libra, Massimo ;

McCubrey, James A. .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2016, 1863 (03) :438-448

[8] Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer [J].

Candido, Saverio ;

Maestro, Roberta ;

Polesel, Jerry ;

Catania, Alessia ;

Maira, Francesca ;

Signorelli, Santo S. ;

McCubrey, James A. ;

Libra, Massimo .

ONCOTARGET, 2014, 5 (06) :1576-1594

[9] The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer [J].

Chakraborty, Subhankar ;

Kaur, Sukhwinder ;

Guha, Sushovan ;

Batra, Surinder K. .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2012, 1826 (01) :129-169

[10] WNT-1 inducible signaling pathway protein-1 enhances growth and tumorigenesis in human breast cancer [J].

Chiang, Kun-Chun ;

Yeh, Chun-Nan ;

Chung, Li-Chuan ;

Feng, Tsui-Hsia ;

Sun, Chi-Chin ;

Chen, Miin-Fu ;

Jan, Yi-Yin ;

Yeh, Ta-Sen ;

Chen, Shin-Cheh ;

Juang, Horng-Heng .

SCIENTIFIC REPORTS, 2015, 5

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