Open AccessGeneration and characterization of hepatocellular carcinoma cell lines with enhanced cancer stem cell potential
Author(s) -
Muenzner Julienne K.,
Kunze Philipp,
Lindner Pablo,
Polaschek Sandra,
Menke Kira,
Eckstein Markus,
Geppert Carol I.,
Chanvorachote Pithi,
Baeuerle Tobias,
Hartmann Arndt,
SchneiderStock Regine
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13911
Subject(s) - hepatocellular carcinoma , cancer stem cell , cancer research , cancer , metastasis , stem cell , liver cancer , biology , cell culture , cancer cell , cell , carcinogenesis , medicine , pathology , microbiology and biotechnology , genetics
Hepatocellular carcinoma ( HCC ) is one of the most common causes for cancer‐related death worldwide with rapidly increasing incidence and mortality rates. As for other types of cancers, also in HCC cancer stem cells ( CSC s) are thought to be responsible for tumour initiation, progression and therapy failure. However, as rare subpopulations of tumour tissue, CSC s are difficult to isolate, thus making the development of suitable and reliable model systems necessary. In our study, we generated HepG2 subclones with enriched CSC potential by application of the spheroid formation method and subsequent single‐cell cloning. Analyses in several 2D and 3D cell culture systems as well as a panel of functional assays both in vitro and in vivo revealed that the generated subclones displayed characteristic and sustained features of tumour initiating cells as well as highly aggressive properties related to tumour progression and metastasis. These characteristics could clearly be correlated with the expression of CSC markers that might have prognostic value in the clinical HCC setting. Therefore, we conclude that our CSC enriched HepG2 clones certainly represent suitable model systems to study the role of CSC s during HCC initiation, progression and drug resistance.