Premium
A novel human hepatoma cell line, FLC‐4, exhibits highly enhanced liver differentiation functions through the three‐dimensional cell shape
Author(s) -
Laurent Thomas,
Murase Daiki,
Tsukioka Sayaka,
Matsuura Tomokazu,
Nagamori Seishi,
Oda Hiroaki
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.23033
Subject(s) - extracellular matrix , microbiology and biotechnology , cell culture , cell , liver cell , hepatocyte , extracellular , actin , cellular differentiation , biology , cell type , gene expression , gene , biochemistry , in vitro , genetics , medicine
We characterized three‐dimensional human hepatoma cell lines, functional liver cell (FLC) cell lines, to establish a highly differentiated hepatoma cell line. We investigated the effect of extracellular matrix and cell morphology on liver‐specific gene expression in FLC cells. The hepatocyte nuclear factor‐4α (HNF‐4α) and other liver‐specific gene expressions were enhanced in spherical FLC‐4 cells on EHS‐gel, but other human hepatoma cells such as HepG2 did not show the enhancement. Importantly, the liver‐specific gene expression levels in spherical FLC‐4 cells cultured on EHS‐gel were comparable to those of human liver and were much higher than those of other human hepatoma cell lines. The major matrix components and growth factors in EHS‐gel did not affect cell shape and liver functions. To exclude any effect of the extracellular matrix, we made spherical FLC‐4 cells by actin filament disruption. The actin‐disrupted spherical cells also showed an enhanced liver‐specific gene expression. We concluded that three‐dimensional cell shape per se is one of the most important determinants of liver differentiation functions in FLC‐4 cells. Cell morphology‐dependent induction of liver‐specific gene expression was mediated through microtubule organization. In conclusion, differentiation of FLC‐4 human hepatoma cell line can be enhanced to a human liver‐like level through the three‐dimensional cell shape in a microtubule‐dependent manner. J. Cell. Physiol. 227: 2898–2906, 2012. © 2011 Wiley Periodicals, Inc.