E-cadherin protects primary hepatocyte spheroids from cell death by a caspase-independent mechanism

Jennifer L. Luebke-Wheeler, Geir Nedredal, Le Yee, Bruce P. Amiot, Scott L. Nyberg

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1281-1287
Number of pages7
JournalCell transplantation
Issue number12
StatePublished - 2009


  • Anoikis
  • Caspase-independent cell death
  • E-cadherin
  • Hepatocyte spheroids

ASJC Scopus subject areas

  • Medicine(all)


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