Mouse models of nonmelanoma skin cancer

The skin is the largest organ of the mammalian body, made up of multiple layers, which include the epidermis, dermis, and subcutis (Alam and Ratner, N Engl J Med 344(13):975-983, 2001). The human interfollicular epidermis can be subdivided into five different layers: (1) stratum basale, (2) stratum spinosum, (3) stratum granulosum, (4) stratum lucidum, and (5) stratum corneum, all originating from basal keratinocytes by differentiation (Hameetman et al., BMC cancer 13:58, 2013; Ramirez et al., Differentiation 58(1):53-64, 1994). The epidermis is also able to generate different appendages: hair follicles (HF) and their associated sebaceous glands (Sibilia et al., Cell 102(2):211-220, 2000) as well as sweat glands (Luetteke et al., Genes Dev 8(4):399-413, 1994). The skin has important functions in several biological processes like environmental barrier, tissue regeneration, hair cycling, and wound repair. During these processes, stem cells from the interfollicular epidermis and from the hair follicle bulge are activated to renew the epidermis or hair. The epidermis and hair undergo continuous homeostatic regeneration and mutations, upon mutations which disturb the balance of homeostatic regeneration of epidermis and hair and lead to enhanced proliferation of keratinocytes, development of skin cancer is developed. Tumors that arise in the skin are mainly of three types: malignant melanoma, arising from melanocytes, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), the latter two both arising from keratinocytes or hair follicle cells. In this chapter, we will describe some genetically engineered mouse models (GEMM) that aim at modeling human BCC and SCC and their respective precancerous lesions. We will describe the experimental approaches used in our laboratory to analyze tumor-bearing mice focusing on methods necessary for the induction of tumor growth as well as for the molecular and histological analysis of tumor tissue.