Open AccessNemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by malignant HaCaT cells
Author(s) -
Räsänen Kati,
Salmenperä Pertteli,
Baumann Marc,
Virtanen Ismo,
Vaheri Antti
Publication year - 2008
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2008.09.002
Subject(s) - hacat , fibroblast , keratinocyte , chemistry , cancer research , carcinogenesis , cell culture , cell , dermal fibroblast , microbiology and biotechnology , biology , in vitro , biochemistry , genetics , gene
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.