Nemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by malignant HaCaT cells.
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.
Räsänen
Kati
K
Haartman Institute, POB 21, FI-00014 University of Helsinki, Finland. kati.rasanen@helsinki.fi
Salmenperä
Pertteli
P
Baumann
Marc
M
Virtanen
Ismo
I
Vaheri
Antti
A
D002448:Cell Adhesion; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology*; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D012878:Skin Neoplasms / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology*; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C066855:HGF protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2