The Role of Endogenous Factors in Skin Carcinogenesis

Abstract

Based upon clinical experience Virchow introduced the concept of irritation-induced carcinogenesis in 1862 (Virchow 1863). Since then a significant body of information has been accumulated providing evidence for an intimate relationship between wounding, wound healing, and tumor development. It includes medical case reports suggesting an influence of injury or chronic irritation on human carcinogenesis (Mueller and Thornbury 1973; Sanderson and Mackie 1979) and results from several experimental models indicating that wounding, although not of itself a carcinogenic stimulus (Hasegawa et al. 1987), can act as a tumor promoter in animals exposed to initiating chemical or viral carcinogens. Thus, sarcomas develop at the site of experimental wounds in chickens infected with Rous sarcoma virus (Dolberg et al. 1985) and in v-jun transgenic mice (Schuh et al. 1990). Moreover, epidermal tumors arise at sites of increased mechanical stress in v-ras transgenic mice (Bailleul et al. 1990; Leder et al. 1990). Upon initiation with chemical carcinogens wounding induces tumor development in mouse and rat liver (Fisher and Fisher 1959: Pound and McGuirre 1978), in rat intestine (Pozharizski 1975; Chester et al. 1989), in mouse oral mucosa (Konstantinides and Smulov 1982), in rabbit ear (McKenzie and Rous 1941), and in mouse skin (Hennings and Boutwell 1970; Clark-Lewis and Murray 1978; Argyris 1980). More recently, a variety of growth factors which are produced and released in a temporarily and locally restricted manner during the wound response have been found to be constitutively expressed in tumor cells and to support tumor growth via an autocrine activation pathway (for review see Sporn and Roberts 1986; Heldin and Westermark 1989).