Pancreatic stellate cells increase pancreatic cancer cells invasion through the hepatocyte growth factor /c-Met/survivin regulated by P53/P21

被引：36

作者：

Yang, Xiao-Peng ^{[1
]}

Liu, Shang-Long ^{[2
]}

Xu, Jian-Fei ^{[1
]}

Cao, Shou-Gen ^{[2
]}

Li, Yu ^{[2
]}

Zhou, Yan-Bing ^{[1
,2
]}

机构：

[1] Qingdao Univ, Dept Clin Med, Med Coll, Qingdao, Shandong, Peoples R China

[2] Qingdao Univ, Affiliated Hosp, Dept Gen Surg, 16 Jiang Su St, Qingdao, Shandong, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2017年 / 357卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Pancreatic stellate cells; HGF/c-Met; Survivin; P53; P21; EPITHELIAL-MESENCHYMAL TRANSITION; MET SIGNALING PATHWAY; TUMOR MICROENVIRONMENT; GENOMIC INSTABILITY; SURVIVIN EXPRESSION; NEGATIVE REGULATION; P53; METASTASIS; CHEMORESISTANCE; MUTATIONS;

D O I：

10.1016/j.yexcr.2017.04.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic stellate cells (PSCs) are a key cellular component of the pancreatic tumor microenvironment and are considered to contribute to tumor invasion and metastasis. Multiple cytokines and growth factors derived from PSCs are involved in malignant cancer progression, including hepatocyte growth factor (HGF). However, the molecular mechanisms by which HGF regulates cancer invasion and metastasis have not been completely elucidated. Here, we report that two pancreatic cancer (PC) cell lines, Panc-1 and SW1990, displayed different invasive and migratory abilities after treatment with HGF secreted by PSCs. We found that HGF enhanced the invasive and migratory capacity of Panc-1 cells because of P53 deficiency, leading to overexpression of c-Met, which was regulated through P21. Additionally, our data showed that HGF/c-Met-mediated invasion and migration required the upregulation of survivin expression. In conclusion, PSCs promote PC cells invasion and migration via the HGF/c-Met/survivin pathway, which is negatively regulated by P53/P21.

引用

页码：79 / 87

页数：9

共 45 条

[1] Validating survivin as a cancer therapeutic target [J].

Altieri, DC .

NATURE REVIEWS CANCER, 2003, 3 (01) :46-54

[2]

Amos Keith D., 2006, Proceedings of the American Association for Cancer Research Annual Meeting, V47, P396

[3] A Starring Role for Stellate Cells in the Pancreatic Cancer Microenvironment [J].

Apte, Minoti V. ;

Wilson, Jeremy S. ;

Lugea, Aurelia ;

Pandol, Stephen J. .

GASTROENTEROLOGY, 2013, 144 (06) :1210-1219

[4] p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells [J].

Armesilla-Diaz, Alejandro ;

Elvira, Gema ;

Silva, Augusto .

EXPERIMENTAL CELL RESEARCH, 2009, 315 (20) :3598-3610

[5] Survivin expression in pancreatic intraepithelial neoplasia (PanIN):: Steady increase along the developmental stages of pancreatic ductal adenocarcinoma [J].

Bhanot, Uniesh ;

Heydrich, Rene ;

Moeller, Peter ;

Hasel, Cornelia .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2006, 30 (06) :754-759

[6]

Bükki J, 2014, NEW ENGL J MED, V371, P2139, DOI 10.1056/NEJMc1412266

[7] Characterization of mutations and loss of heterozygosity of p53 and K-ras2 in pancreatic cancer cell lines by immobilized polymerase chain reaction -: art. no. 11 [J].

Butz, J ;

Wickstrom, E ;

Edwards, J .

BMC BIOTECHNOLOGY, 2003, 3 (1)

[8]

Campbell C., 2003, ROLE GALECTIN 3 SURV

[9] The patterns and dynamics of genomic instability in metastatic pancreatic cancer [J].

Campbell, Peter J. ;

Yachida, Shinichi ;

Mudie, Laura J. ;

Stephens, Philip J. ;

Pleasance, Erin D. ;

Stebbings, Lucy A. ;

Morsberger, Laura A. ;

Latimer, Calli ;

McLaren, Stuart ;

Lin, Meng-Lay ;

McBride, David J. ;

Varela, Ignacio ;

Nik-Zainal, Serena A. ;

Leroy, Catherine ;

Jia, Mingming ;

Menzies, Andrew ;

Butler, Adam P. ;

Teague, Jon W. ;

Griffin, Constance A. ;

Burton, John ;

Swerdlow, Harold ;

Quail, Michael A. ;

Stratton, Michael R. ;

Iacobuzio-Donahue, Christine ;

Futreal, P. Andrew .

NATURE, 2010, 467 (7319) :1109-1113

[10] c-Met signaling in the development of tumorigenesis and chemoresistance: Potential applications in pancreatic cancer [J].

Delitto, Daniel ;

Vertes-George, Eva ;

Hughes, Steven J. ;

Behrns, Kevin E. ;

Trevino, Jose G. .

WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (26) :8458-8470

← 1 2 3 4 5 →