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Behavior of a cell line derived from normal human hepatocytes on non-physiological and physiological-type substrates: Evidence for enhancement of secretion of liver-specific proteins by a three-dimensional growth pattern

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Summary

The behavior of a recently described cell line, HH25, derived from normal human hepatocytes, has been investigated on several different substrates—tissue-culture plastic, glass, a thin layer of rat-tail collagen I, and thin layers or thick gels of extracellular matrix derived from the Engelbreth-Holm-Swarm murine sarcoma (EHS matrix). Cellular morphology, proliferation, and secretion of three hepatocyte-specific proteins (albumin, α1 acid glycoprotein, and α1 antitrypsin) have been examined. There were no differences in morphology, proliferation, or differentiated function in the cells on either plastic, glass, collagen, I, or a thin layer of EHS matrix, but on a thick EHS matrix gel the cells altered their morphology (forming three-dimensional colonies with canalicular-like structures) and their production of albumin and α1 acid glycoprotein was enhanced. This suggests that the enhanced differentiated function is associated with the morphological change (occurring only on the thick EHS gel) rather than with receptor-mediated cell-matrix interactions (which can also occur on the thin layer of EHS matrix). This cell line is therefore a good in vitro cellular model for the investigation of the roles of morphological changes and of cell-cell and cell-matrix interactions in the control of human hepatocyte behavior without the need for an extensive source of primary tissue.

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Author notes

  1. Matthew Smalley

    Present address: Section of Cell Biology and Experimental Pathology, Haddow Laboratories, Institute of Cancer Research, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, United Kingdom

Authors and Affiliations

  1. Liver Group Laboratory, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, W12 0NN, London, United Kingdom

    Matthew Smalley, Kenneth Leiper, David Floyd, Clare Selden & Humphrey Hodgson

  2. Electron Microscopy Unit, Department of Pathology, Queen Charlotte’s and Chelsea Hospital, Goldhawk Road, W6 0XG, London, United Kingdom

    Margaret Mobberley & Tim Ryder

  3. Division of Gastroenterology and Nutrition, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada

    Eve A. Roberts

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  1. Matthew Smalley
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  2. Kenneth Leiper
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  3. David Floyd
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  4. Margaret Mobberley
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  6. Clare Selden
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  7. Eve A. Roberts
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  8. Humphrey Hodgson
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Smalley, M., Leiper, K., Floyd, D. et al. Behavior of a cell line derived from normal human hepatocytes on non-physiological and physiological-type substrates: Evidence for enhancement of secretion of liver-specific proteins by a three-dimensional growth pattern. In Vitro Cell.Dev.Biol.-Animal 35, 22–32 (1999). https://doi.org/10.1007/s11626-999-0040-6

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  • DOI: https://doi.org/10.1007/s11626-999-0040-6

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