Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma

被引:31
作者
Ishii, Takamichi [1 ,2 ]
Yasuchika, Kentaro [2 ]
Suemori, Hirofumi
Nakatsuji, Norio [3 ,4 ]
Ikai, Iwao [2 ,5 ]
Uemoto, Shinji [2 ]
机构
[1] Kyoto Univ, Inst Frontier Med Sci, Stem Cell Res Ctr, Lab Embryon Stem Cell Res,Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto 6068507, Japan
[3] Kyoto Univ, Inst Integrated Cell Mat Sci, Kyoto 6068507, Japan
[4] Kyoto Univ, Inst Frontier Med Sci, Dept Dev & Differentiat, Kyoto 6068507, Japan
[5] Natl Hosp Org, Kyoto Med Ctr, Dept Surg, Kyoto, Japan
关键词
Cancer stem cell; Cholangiocarcinoma; AFP; Notch; ICC; EMBRYONIC STEM-CELLS; PROSPECTIVE IDENTIFICATION; LIVER-CANCER; DIFFERENTIATION; HEPATOCYTES; MATURATION; MARKERS; TARGET; MICE;
D O I
10.1016/j.canlet.2010.01.019
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We aimed to demonstrate that alpha-fetoprotein (AFP)-producing cells in cholangiocarcinomas possessed cancer stem cell (CSC)-like properties. AFP enhancer/promoter-driven EGFP gene was transfected into human cholangiocarcinoma cell lines. One cell line, RBE, expressed both AFP and EGFP. Clonal analyses revealed that one EGFP-positive cell generated both EGFP-positive and EGFP-negative cell fractions. However, one EGFP-negative cell never produced EGFP-positive cells. The EGFP-positive cells had a greater tumorigenic potential. Only the EGFP-positive cells expressed Notch1. AFP and Notch1 expression was observed in clinical intrahepatic cholangiocarcinomas. The AFP-producing cells were suggested to be CSCs. The Notch pathway might play an important role in maintaining the CSC characteristics. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:25 / 34
页数:10
相关论文
共 29 条
[1]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[2]   Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[3]   Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties [J].
Chiba, Tetsuhiro ;
Kita, Kaoru ;
Zheng, Yun-Wen ;
Yokosuka, Osamu ;
Saisho, Hiromitsu ;
Iwama, Atsushi ;
Nakauchi, Hiromitsu ;
Taniguchi, Hideki .
HEPATOLOGY, 2006, 44 (01) :240-251
[4]   Prospective identification of tumorigenic prostate cancer stem cells [J].
Collins, AT ;
Berry, PA ;
Hyde, C ;
Stower, MJ ;
Maitland, NJ .
CANCER RESEARCH, 2005, 65 (23) :10946-10951
[5]   Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium [J].
Crosby, HA ;
Kelly, DA ;
Strain, AJ .
GASTROENTEROLOGY, 2001, 120 (02) :534-544
[6]   Tumour stem cells and drug resistance [J].
Dean, M ;
Fojo, T ;
Bates, S .
NATURE REVIEWS CANCER, 2005, 5 (04) :275-284
[7]  
Enjoji M, 1997, IN VITRO CELL DEV-AN, V33, P681
[8]   Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells [J].
Fausto, N .
HEPATOLOGY, 2004, 39 (06) :1477-1487
[9]   Cholangiocarcinoma: Current concepts and insights [J].
Gores, GJ .
HEPATOLOGY, 2003, 37 (05) :961-969
[10]   Thy1-positive mesenchymal cells promote the maturation of CD49f-positive hepatic progenitor cells in the mouse fetal liver [J].
Hoppo, T ;
Fujii, H ;
Hirose, T ;
Yasuchika, K ;
Azuma, H ;
Baba, S ;
Naito, M ;
Machimoto, T ;
Ikai, I .
HEPATOLOGY, 2004, 39 (05) :1362-1370