Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells

被引：93

作者：

Masamune, Atsushi ^{[1
]}

Yoshida, Naoki ^{[1
]}

Hamada, Shin ^{[1
]}

Takikawa, Tetsuya ^{[1
]}

Nabeshima, Tatsuhide ^{[1
]}

Shimosegawa, Tooru ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 495卷 / 01期

关键词：

Fibrosis; microRNA; Myofibroblast; Pancreatitis; Stroma; Tumor microenvironment; EXTRACELLULAR VESICLES; MICRORNA-SIGNATURE; PROLIFERATION; PROTEIN; ROLES;

D O I：

10.1016/j.bbrc.2017.10.141

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：

Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of a-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor beta 1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：71 / 77

页数：7

共 41 条

[1] 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

[2] Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review [J].

Azmi, Asfar S. ;

Bao, Bin ;

Sarkar, Fazlul H. .

CANCER AND METASTASIS REVIEWS, 2013, 32 (3-4) :623-642

[3] Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells [J].

Bachem, MG ;

Schünemann, M ;

Ramadani, M ;

Siech, M ;

Beger, H ;

Buck, A ;

Zhou, SX ;

Schmid-Kotsas, A ;

Adler, G .

GASTROENTEROLOGY, 2005, 128 (04) :907-921

[4] Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts [J].

Chowdhury, Ridwana ;

Webber, Jason P. ;

Gurney, Mark ;

Mason, Malcolm D. ;

Tabi, Zsuzsanna ;

Clayton, Aled .

ONCOTARGET, 2015, 6 (02) :715-731

[5] Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver [J].

Costa-Silva, Bruno ;

Aiello, Nicole M. ;

Ocean, Allyson J. ;

Singh, Swarnima ;

Zhang, Haiying ;

Thakur, Basant Kumar ;

Becker, Annette ;

Hoshino, Ayuko ;

Mark, Milica Tesic ;

Molina, Henrik ;

Xiang, Jenny ;

Zhang, Tuo ;

Theilen, Till-Martin ;

Garcia-Santos, Guillermo ;

Williams, Caitlin ;

Ararso, Yonathan ;

Huang, Yujie ;

Rodrigues, Goncalo ;

Shen, Tang-Long ;

Labori, Knut Jorgen ;

Lothe, Inger Marie Bowitz ;

Kure, Elm H. ;

Hernandez, Jonathan ;

Doussot, Alexandre ;

Ebbesen, Saya H. ;

Grandgenett, Paul M. ;

Hollingsworth, Michael A. ;

Jain, Maneesh ;

Mallya, Kavita ;

Batra, Surinder K. ;

Jarnagin, William R. ;

Schwartz, Robert E. ;

Matei, Irina ;

Peinado, Hector ;

Stanger, Ben Z. ;

Bromberg, Jacqueline ;

Lyden, David .

NATURE CELL BIOLOGY, 2015, 17 (06) :816-+

[6] Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p [J].

Ding, Guoping ;

Zhou, Liangjing ;

Qian, Yingming ;

Fu, Mingnian ;

Chen, Jian ;

Chen, Jionghuang ;

Xiang, Jianyang ;

Wu, Zhengrong ;

Jiang, Guixing ;

Cao, Liping .

ONCOTARGET, 2015, 6 (30) :29877-29888

[7] Extracellular vesicles: biology and emerging therapeutic opportunities [J].

EL Andaloussi, Samir ;

Maeger, Imre ;

Breakefield, Xandra O. ;

Wood, Matthew J. A. .

NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (05) :348-358

[8] StellaTUM: current consensus and discussion on pancreatic stellate cell research [J].

Erkan, Mert ;

Adler, Guido ;

Apte, Minoti V. ;

Bachem, Max G. ;

Buchholz, Malte ;

Detlefsen, Soenke ;

Esposito, Irene ;

Friess, Helmut ;

Gress, Thomas M. ;

Habisch, Hans-Joerg ;

Hwang, Rosa F. ;

Jaster, Robert ;

Kleeff, Joerg ;

Kloeppel, Guenter ;

Kordes, Claus ;

Logsdon, Craig D. ;

Masamune, Atsushi ;

Michalski, Christoph W. ;

Oh, Junseo ;

Phillips, Phoebe A. ;

Pinzani, Massimo ;

Reiser-Erkan, Carolin ;

Tsukamoto, Hidekazu ;

Wilson, Jeremy .

GUT, 2012, 61 (02) :172-178

[9] Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury [J].

Gatti, Stefano ;

Bruno, Stefania ;

Deregibus, Maria Chiara ;

Sordi, Andrea ;

Cantaluppi, Vincenzo ;

Tetta, Ciro ;

Camussi, Giovanni .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2011, 26 (05) :1474-1483

[10] IL-6/STAT3 Plays a Regulatory Role in the Interaction Between Pancreatic Stellate Cells and Cancer Cells [J].

Hamada, Shin ;

Masamune, Atsushi ;

Yoshida, Naoki ;

Takikawa, Tetsuya ;

Shimosegawa, Tooru .

DIGESTIVE DISEASES AND SCIENCES, 2016, 61 (06) :1561-1571

← 1 2 3 4 5 →