Molecular Oncology
Volume 2, Issue 4 , Pages 340-348, December 2008

Nemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by malignant HaCaT cells

  • Kati Räsänen

      Affiliations

    • Haartman Institute, POB 21, FI-00014 University of Helsinki, Finland
    • Corresponding Author InformationCorresponding author. Tel.: +358 9 1912 6608; fax: +358 9 1912 6491.
    • ,
  • Pertteli Salmenperä

      Affiliations

    • Haartman Institute, POB 21, FI-00014 University of Helsinki, Finland
    • ,
  • Marc Baumann

      Affiliations

    • Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland
    • ,
  • Ismo Virtanen

      Affiliations

    • Institute of Biomedicine/Anatomy, POB 63, FI-00014 University of Helsinki, Finland
    • ,
  • Antti Vaheri

      Affiliations

    • Haartman Institute, POB 21, FI-00014 University of Helsinki, Finland

Received 5 August 2008; received in revised form 11 September 2008; accepted 14 September 2008. published online 17 October 2008.

Abstract 

Cell–cell clustering of fibroblasts, called nemosis, leads to a massive growth factor, proteolytic and proinflammatory response. Culturing fibroblasts in conditioned medium collected from HaCaT keratinocyte cell panel representing different stages of skin carcinogenesis had a differential effect on fibroblast nemosis. Non-malignant keratinocytes had a nemosis-inhibiting effect on fibroblasts as seen by inhibition of COX-2 protein expression. Conditioned medium from malignant cells promoted fibroblast nemosis by inducing higher levels of COX-2, HGF/SF and VEGF. Even a small amount of malignant medium converted the inhibitory effect of benign medium, whereas non-malignant medium neutralized the nemosis-promoting effect of malignant medium. In collagen co-cultures benign keratinocytes caused a nemosis-inhibiting effect on fibroblast spheroids by inhibiting COX-2 induction, while with malignant keratinocytes myofibroblastic differentiation of fibroblasts was seen.

Keywords: Nemosis, Fibroblast, Keratinocyte, Growth factors

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PII: S1574-7891(08)00122-1

doi:10.1016/j.molonc.2008.09.002

Molecular Oncology
Volume 2, Issue 4 , Pages 340-348, December 2008

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