Alterations in epidermal sulfated proteoglycan production following topical application of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate to mouse skin.
Topical application of the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin causes marked changes in epidermal cell growth and differentiation. In the present studies we characterized the production of sulfated proteoglycans in the epidermis following treatment with TPA since these macromolecules are important structural and functional components of the tissue. We found that 35S-sulfate was readily incorporated into mouse epidermal proteoglycans. Sepharose CL-4B column chromatography revealed one major peak of sulfated proteoglycans in this tissue (Kav = 0.4-0.5). Approximately 65% of these proteoglycans were heparan sulfate and 10-20% chondroitin sulfate. Using specific monoclonal antibodies and flow cytometry, we found that the epidermal cells produced chondroitin-4-sulfate, chondroitin-6-sulfate and chondroitin-O-sulfate. Within 24 hr of application of TPA to mice, an increase in glycosaminoglycan content of the epidermis was observed. This was associated with a decrease in 35S-sulfate uptake into the tissue. Although TPA had no effect on the size or relative distribution of the epidermal sulfated proteoglycans, an increase in chondroitin-4-sulfate expression was observed in treated skin. Changes in the production of proteoglycans following TPA treatment may underlie structural alterations that occur in the epidermis during tumor promotion.
Laskin
J D
JD
Department of Environmental, UMDNJ-Robert Wood Johnson Medical School.
Dokidis
A
A
Laskin
D L
DL
D000818:Animals; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D005260:Female; D006497:Heparan Sulfate / Q000096:biosynthesis; D051379:Mice; D011509:Proteoglycans / Q000096:biosynthesis*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D011509:Proteoglycans; D013755:Tetradecanoylphorbol Acetate