Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling

被引:53
作者
Liu, Yang [1 ]
Li, Fan [1 ]
Gao, Feng [1 ]
Xing, Lingxi [1 ]
Qin, Peng [2 ]
Liang, Xingxin [1 ]
Zhang, Jiajie [1 ]
Qiao, Xiaohui [1 ]
Lin, Lizhou [1 ]
Zhao, Qian [3 ,4 ]
Du, Lianfang [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Ultrasound, Shanghai 200080, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Instrument Sci & Engn, Shanghai 200240, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol, Shanghai 200025, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Natl Minist Educ, Shanghai 200025, Peoples R China
基金
中国国家自然科学基金;
关键词
periostin; pancreatic cancer; angiogenesis; Erk; VEGF; GASTRIC-CANCER; STELLATE CELLS; METASTASIS; STROMA; VEGF; GEMCITABINE; INHIBITION; EXPRESSION; CARCINOMA; THERAPY;
D O I
10.18632/oncotarget.9512
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pancreatic cancer (PaC) consists of a bulk of stroma cells which contribute to tumor progression by releasing angiogenic factors. Recent studies have found that periostin (POSTN) is closely associate with the metastatic potential and prognosis of PaC. The purpose of this study is to determine the role of POSTN in tumor angiogenesis and explore the precise mechanisms. In this study, we used lentiviral shRNA and human recombinant POSTN protein (rPOSTN) to negatively and positively regulate POSTN expression in vitro. We found that increased POSTN expression promoted the tubule formation dependent on human umbilical vein endothelial cells (HUVECs). Moreover, knockdown of POSTN in PaC cells reduced tumor growth and VEGF expression in vivo. In accordance with these observations, we found that Erk phosphorylation and its downstream VEGF expression were upregulated achieved in rPOSTN-treated groups, opposing results were obversed in POSTN-slienced group. Meanwhile, Erk inhibitor SCH772984 significantly decreased VEGF expression as well as tubule formation of HUVECs in rPOSTN-treated PaC cells. Taken together, these findings suggest that POSTN promotes tumor angiogenesis via Erk/VEGF signaling in PaC and POSTN may be a new target for cancer anti-vascular treatment.
引用
收藏
页码:40148 / 40159
页数:12
相关论文
共 43 条
[1]   Antiangiogenic therapy and tumor progression [J].
Blagosklonny, MV .
CANCER CELL, 2004, 5 (01) :13-17
[2]   How Avastin potentiates chemotherapeutic drugs - Action and reaction in antiangiogenic therapy [J].
Blagosklonny, MV .
CANCER BIOLOGY & THERAPY, 2005, 4 (12) :1307-1310
[3]   Angiogenesis in cancer and other diseases [J].
Carmeliet, P ;
Jain, RK .
NATURE, 2000, 407 (6801) :249-257
[4]   Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop [J].
Coffman, Lan G. ;
Choi, Yun-Jung ;
McLean, Karen ;
Allen, Benjamin L. ;
di Magliano, Marina Pasca ;
Buckanovich, Ronald J. .
ONCOTARGET, 2016, 7 (06) :6916-6932
[5]   VEGF expression in pancreatic cancer and other malignancies: a review of the literature [J].
Costache, M. I. ;
Ioana, Mihai ;
Iordache, Sevastita ;
Ene, D. ;
Costache, Cornelia Alexandra ;
Saftoiu, A. .
ROMANIAN JOURNAL OF INTERNAL MEDICINE, 2015, 53 (03) :199-208
[6]  
Craven KE, 2015, CANC LETT
[7]   Adjuvant and neoadjuvant therapies in resectable pancreatic cancer: a systematic review of randomized controlled trials [J].
D'Angelo, Francesco A. ;
Antolino, Laura ;
La Rocca, Mara ;
Petrucciani, Niccolo ;
Magistri, Paolo ;
Aurello, Paolo ;
Ramacciato, Giovanni .
MEDICAL ONCOLOGY, 2016, 33 (03) :1-9
[8]   VEGF signaling inside vascular endothelial cells and beyond [J].
Eichmann, Anne ;
Simons, Michael .
CURRENT OPINION IN CELL BIOLOGY, 2012, 24 (02) :188-193
[9]   Periostin creates a tumor-supportive microenvironment in the pancreas by sustaining fibrogenic stellate cell activity [J].
Erkan, Mert ;
Kleeff, Joerg ;
Gorbachevski, Andre ;
Reiser, Carolin ;
Mitkus, Tomas ;
Esposito, Irene ;
Giese, Thomas ;
Buechler, Markus W. ;
Giese, Nathalia A. ;
Friess, Helmut .
GASTROENTEROLOGY, 2007, 132 (04) :1447-1464
[10]   The role of stroma in pancreatic cancer: diagnostic and therapeutic implications [J].
Erkan, Mert ;
Hausmann, Simone ;
Michalski, Christoph W. ;
Fingerle, Alexander A. ;
Dobritz, Martin ;
Kleeff, Joerg ;
Friess, Helmut .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2012, 9 (08) :454-467