TY - JOUR
T1 - E-cadherin protects primary hepatocyte spheroids from cell death by a caspase-independent mechanism
AU - Luebke-Wheeler, Jennifer L.
AU - Nedredal, Geir
AU - Yee, Le
AU - Amiot, Bruce P.
AU - Nyberg, Scott L.
PY - 2009
Y1 - 2009
N2 - Cultivation of primary hepatocytes as spheroids creates an efficient three-dimensional model system for hepatic studies in vitro and as a cell source for a spheroid reservoir bioartificial liver. The mechanism of spheroid formation is poorly understood, as is an explanation for why normal, anchorage-dependent hepatocytes remain viable and do not undergo detachment-induced apoptosis, known as anoikis, when placed in suspension spheroid culture. The purpose of this study was to investigate the role of E-cadherin, a calciumdependent cell adhesion molecule, in the formation and maintenance of hepatocyte spheroids. Hepatocyte spheroids were formed by a novel rocker technique and cultured in suspension for up to 24 h. The dependence of spheroid formation on E-cadherin and calcium was established using an E-cadherin blocking antibody and a calcium chelator. We found that inhibiting E-cadherin prevented cell-cell attachment and spheroid formation, and, surprisingly, E-cadherin inhibition led to hepatocyte death through a caspase-independent mechanism. In conclusion, E-cadherin is required for hepatocyte spheroid formation and may be responsible for protecting hepatocytes from a novel form of caspase-independent cell death.
AB - Cultivation of primary hepatocytes as spheroids creates an efficient three-dimensional model system for hepatic studies in vitro and as a cell source for a spheroid reservoir bioartificial liver. The mechanism of spheroid formation is poorly understood, as is an explanation for why normal, anchorage-dependent hepatocytes remain viable and do not undergo detachment-induced apoptosis, known as anoikis, when placed in suspension spheroid culture. The purpose of this study was to investigate the role of E-cadherin, a calciumdependent cell adhesion molecule, in the formation and maintenance of hepatocyte spheroids. Hepatocyte spheroids were formed by a novel rocker technique and cultured in suspension for up to 24 h. The dependence of spheroid formation on E-cadherin and calcium was established using an E-cadherin blocking antibody and a calcium chelator. We found that inhibiting E-cadherin prevented cell-cell attachment and spheroid formation, and, surprisingly, E-cadherin inhibition led to hepatocyte death through a caspase-independent mechanism. In conclusion, E-cadherin is required for hepatocyte spheroid formation and may be responsible for protecting hepatocytes from a novel form of caspase-independent cell death.
KW - Anoikis
KW - Caspase-independent cell death
KW - E-cadherin
KW - Hepatocyte spheroids
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UR - http://www.scopus.com/inward/citedby.url?scp=77349116653&partnerID=8YFLogxK
U2 - 10.3727/096368909X474258
DO - 10.3727/096368909X474258
M3 - Article
C2 - 20003757
AN - SCOPUS:77349116653
SN - 0963-6897
VL - 18
SP - 1281
EP - 1287
JO - Cell transplantation
JF - Cell transplantation
IS - 12
ER -