Enhancement of collagen-degrading enzymes in the dermis after one topical application of tumor-promoting phorbol esters.

The effect of tumor-promoting and non-promoting skin mitogens on the induction of matrix degradation in the dermis of mouse skin has been examined. A stimulation of active collagenolytic and proteolytic enzyme levels was observed after application of the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) as well as the non-promoting skin irritant Ca-ionophore A 23187, but not with the non-irritant mitogen 4-O-methyl-TPA. It therefore appears that the enhancement of collagenolytic and proteolytic enzymes after tumor promoter treatment is mainly due to the inflammation that is always caused by the promoter. However, a subfraction of collagenolytic enzymes that is not extracted from the dermis with 0.5 M NaCl but only with 5 M urea is specifically increased after treatment with TPA and RPA. This fraction is absent in A 23187- or 4-O-methyl-TPA-treated dermis. This indicates that apart from inflammation-induced matrix degradation there is also stimulation of enzymes which are directly related to tumor promotion.