Polyamines and nonmelanoma skin cancer

• Published in: Toxicology and applied pharmacology 2007-11, Vol.224 (3), p.249-256
• Main Author: Gilmour, Susan K.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Biological and medical sciences; BIOSYNTHESIS; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - metabolism; DECARBOXYLASES; Dermatology; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; HEALING; HOMEOSTASIS; Humans; INHIBITION; Medical sciences; METABOLISM; Mice; Mice, Transgenic; Models, Biological; NEOPLASMS; ORNITHINE; Ornithine decarboxylase; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase - metabolism; Ornithine Decarboxylase Inhibitors; Polyamines; Polyamines - metabolism; PUTRESCINE; SKIN; Skin cancer; Skin Neoplasms - enzymology; Skin Neoplasms - metabolism; Skin Neoplasms - prevention & control; Toxicology; TRANSGENIC MICE; Tumors of the skin and soft tissue. Premalignant lesions; WOUNDS
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2006.11.023

Elevated levels of polyamines have long been associated with skin tumorigenesis. Tightly regulated metabolism of polyamines is critical for cell survival and normal skin homeostasis, and these controls are dysregulated in skin tumorigenesis. A key enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC) is upregulated in skin tumors compared to normal skin. Use of transgenic mouse models has demonstrated that polyamines play an essential role in the early promotional phase of skin tumorigenesis. The formation of skin tumors in these transgenic mice is dependent upon polyamine biosynthesis, especially putrescine, since treatment with inhibitors of ODC activity blocks the formation of skin tumors and causes the rapid regression of existing tumors. Although the mechanism by which polyamines promote skin tumorigenesis are not well understood, elevated levels of polyamines have been shown to stimulate epidermal proliferation, alter keratinocyte differentiation status, increase neovascularization, and increase synthesis of extracellular matrix proteins in a manner similar to that seen in wound healing. It is becoming increasingly apparent that elevated polyamine levels activate not only epidermal cells but also underlying stromal cells in the skin to promote the development and progression of skin tumors. The inhibition of polyamine biosynthesis has potential to be an effective chemoprevention strategy for nonmelanoma skin cancer.