The Roles of S100 Proteins and RAGE in Melanoma

The incidence of melanoma continues to rise worldwide and increases annually by 4% to 6% in the United States (Darrell and Rigel 2010). Once metastatic, invasive melanoma offers poor prognosis to patients (Bhatia, Tykodi and Thompson, 2009). The classic prognostic factors in melanoma include primary tumor thickness, patient gender, primary melanoma ulceration, mitotic activity and the presence of tumor infiltrating lymphocytes (Spatz et al. 2010). Besides these established prognostic markers, the S100 protein family member S100B has emerged in recent years as a new prognostic marker and is now incorporated into the American Joint Committee on Cancer (AJCC) melanoma staging system for stage IV melanoma patients (Balch et al. 2009; Chun et al. 2008; Gogas et al. 2009). High S100B serum concentration correlates with poor survival rate (Hauschild et al. 1999). Current studies are also analyzing the prognostic value of S100B in earlier melanoma stages (IIB-III) (Bouwhuis et al. 2010). The role of S100B in the progression of melanoma is not clearly understood. For instance, although it is established that S100B is released from melanoma tumor cells, its role in tumor development, invasion and metastasis is currently under investigation. This chapter will discuss the role of S100B and other members of the S100 protein family in the biology of melanoma. We will focus on the relation between the S100 proteins and their common receptor, the receptor for advanced glycation endproducts (RAGE), in the context of melanoma.