Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

被引:161
作者
Hamada, Shin
Masamune, Atsushi [1 ]
Takikawa, Tetsuya
Suzuki, Noriaki
Kikuta, Kazuhiro
Hirota, Morihisa
Hamada, Hirofumi [2 ]
Kobune, Masayoshi [3 ]
Satoh, Kennichi [4 ]
Shimosegawa, Tooru
机构
[1] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Aoba Ku, Sendai, Miyagi 9808574, Japan
[2] Tokyo Univ Pharm & Life Sci, Dept Life Sci, Lab Oncol, Hachioji, Tokyo 19203, Japan
[3] Sapporo Med Univ, Sch Med, Dept Internal Med 4, Sapporo, Hokkaido, Japan
[4] Miyagi Canc Ctr, Res Inst, Div Canc Stem Cell, Natori, Miyagi 9811293, Japan
基金
日本学术振兴会;
关键词
Stroma; Niche; Cancer stem cells; Fibroblasts; Desmoplastic reaction; METASTASIS; RESISTANCE; FIBROSIS;
D O I
10.1016/j.bbrc.2012.04.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called "cancer stem cells", within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the "stemness" of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:349 / 354
页数:6
相关论文
共 31 条
[1]
Desmoplastic reaction in pancreatic cancer - Role of pancreatic stellate cells [J].
Apte, MV ;
Park, S ;
Phillips, PA ;
Santucci, N ;
Goldstein, D ;
Kumar, RK ;
Ramm, GA ;
Buchler, M ;
Friess, H ;
McCarroll, JA ;
Keogh, G ;
Merrett, N ;
Pirola, R ;
Wilson, JS .
PANCREAS, 2004, 29 (03) :179-187
[2]
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
[3]
RETRACTED: Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells (Retracted article. See vol. 423, pg. 153, 2018) [J].
Bao, Bin ;
Wang, Zhiwei ;
Ali, Shadan ;
Kong, Dejuan ;
Li, Yiwei ;
Ahmad, Aamir ;
Banerjee, Sanjeev ;
Azmi, Asfar S. ;
Miele, Lucio ;
Sarkar, Fazlul H. .
CANCER LETTERS, 2011, 307 (01) :26-36
[4]
Brand Randall E., 1998, Current Opinion in Oncology, V10, P362, DOI 10.1097/00001622-199807000-00014
[5]
Gastrointestinal stem cells [J].
Brittan, M ;
Wright, NA .
JOURNAL OF PATHOLOGY, 2002, 197 (04) :492-509
[6]
Recent advances in cancer stem cells [J].
Cho, Robert W. ;
Clarke, Michael F. .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2008, 18 (01) :48-53
[7]
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
[8]
Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer [J].
Hermann, Patrick C. ;
Huber, Stephan L. ;
Herrler, Tanja ;
Aicher, Alexandra ;
Ellwart, Joachim W. ;
Guba, Markus ;
Bruns, Christiane J. ;
Heeschen, Christopher .
CELL STEM CELL, 2007, 1 (03) :313-323
[9]
Pancreatic Cancer [J].
Hidalgo, Manuel .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (17) :1605-1617
[10]
CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells [J].
Hong, Sung Pil ;
Wen, Jing ;
Bang, Seungmin ;
Park, Seungwoo ;
Song, Si Young .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (10) :2323-2331