| | Nemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by malignant HaCaT cellsReceived 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. a Haartman Institute, POB 21, FI-00014 University of Helsinki, Finland b Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland c Institute of Biomedicine/Anatomy, POB 63, FI-00014 University of Helsinki, Finland Corresponding author. Tel.: +358 9 1912 6608; fax: +358 9 1912 6491.
PII: S1574-7891(08)00122-1 doi:10.1016/j.molonc.2008.09.002 © 2008 Federation of European Biochemical Societies. Published by Elsevier Inc. All rights reserved. | |
|
|