Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma.
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.
Ishii
Takamichi
T
Laboratory of Embryonic Stem Cell Research, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, Japan. taishii@kuhp.kyoto-u.ac.jp
Yasuchika
Kentaro
K
Suemori
Hirofumi
H
Nakatsuji
Norio
N
Ikai
Iwao
I
Uemoto
Shinji
S
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D015415:Biomarkers / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D004742:Enhancer Elements, Genetic; D005260:Female; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014183:Transplantation, Heterologous; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics*
D015415:Biomarkers; D000509:alpha-Fetoproteins; D049452:Green Fluorescent Proteins