Welcome to the MMHCC Skin Cancer Site. At this web site you will find an introduction to human skin cancer followed by more detailed sections on malignant melanoma, squamous cell carcinoma, and basal cell carcinoma. These sections provide information on the clinical findings, histopathology, molecular biology, and mouse models specific to these diseases.

Introduction
Skin cancer is the most prevalent form of human cancer. Over 1 million new cases of skin cancer occur in the United States every year, most of which are either basal cell carcinomas (~900,000 cases/year) or squamous cell carcinoma (~200,000 cases/year) (Miller and Weinstock, 1994). Although the incidence of melanoma is lower (53,600 cases/year), it is the leading cause of skin cancer deaths, causing an estimated 7,400 of the 9,600 skin cancer deaths http://www.cancer.org/downloads.

The skin is a complex organ with several functions including thermoregulation and sensation as well as forming a barrier against fluid loss, chemical exposure, infectious agents, mechanical damage, and ultraviolet radiation. Skin is composed of a several cell types of different embryonic derivation. The ectoderm gives rise to the epidermis, hair follicles, sebaceous, apocrine and eccrine glands and ducts, and nails. The neural crest gives rise to melanocytes, nerves, and sensory receptors, while pilar muscles, fibroblasts, adipocytes, blood and lymph vessels, and cells of the immune system are derived from mesoderm http://skincancer.dermis.net. Regional variation of human skin can be marked with increased numbers of sebaceous glands on the face, numerous eccrine glands and ducts on the palms and soles, and thickened dermis of skin of the back.

Mouse and human skin share many characteristics, but many important differences exist. Human epidermis is about twice as thick as mouse epidermis. Melanocytes in human skin are predominantly located at the junction of epidermis and dermis with some melanocytes present in hair follicles. In mice, melanocytes are predominantly within hair follicles or the interfollicular dermis, but rarely are present at the dermal/epidermal junction. The proportion of skin covered by terminal hair follicles is much higher in mice relative to humans. Eccrine glands are restricted to glabrous skin in mice (footpads), but have a widespread distribution in humans.

The biologic behavior and clinical course of various cutaneous malignancies varies markedly. Basal cell carcinomas are locally invasive, but only very rarely metastasize or cause death. Melanomas on the other hand, are exceptionally metastatic at low tumor burdens and nearly all of the mortality due to melanoma is secondary to metastatic disease. Squamous cell carcinomas occasionally metastasize, but more often are locally invasive.

Many advances in the understanding of tumor invasion and metastasis have occurred in recent years, however, many basic aspects of these processes are still poorly understood (Hanahan and Weinberg, 2000, Yoshida et al., 2000). Much work in tumor biology has employed the powerful methods of tissue culture, however it is difficult to accurately model the complex process of tumor formation and metastasis in vitro. Mouse models of skin cancer in many instances are good approximations of human cancer counterparts and recapitulate the tumor-stromal interactions, angiogenesis, and the multistep nature of tumor progression of many cancers (Van Dyke and Jacks, 2002). These models will also aid in the development and testing of novel therapeutic approaches.

Several approaches of generating and studying mouse skin cancers have been developed. The accessibility of the skin and ease of evaluating skin cancer phenotypes is a major experimental asset and led to the study of topically applied carcinogens nearly 100 years ago. These approaches of chemical carcinogenesis produced a multistep model of squamous cell carcinoma that recapitulated many aspects of the human disease. Exposure to ultraviolet light, an important exposure risk for human melanoma, squamous cell carcinoma, and basal cell carcinoma, has also been used to model these tumors in mice. Organotypic models of skin cancer and xenografting of human tissue onto immunodeficient mice have also been developed and refined recently (Berking and Herlyn, 2001, Maas-Szabowski et al., 2001). Transgenic and knockout mouse strains have been used to model human skin cancer in part because these models have the advantage of examining the effect of genetic changes observed in human malignancy on tumor formation in the mouse (Tietze and Chin, 2000, Brown and Balmain, 1995).

Human Skin Cancer

I. Malignant Melanoma

II.Squamous Cell Carcinoma

III.Basal Cell Carcinoma

References