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.
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
Takamichi
T
Ishii
Kentaro
K
Yasuchika
Hirofumi
H
Suemori
Norio
N
Nakatsuji
Iwao
I
Ikai
Shinji
S
Uemoto
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