A review of the S100 proteins in cancer

Abstract

Aim

In the quest to reduce mortality and morbidity from cancer, there is continued effort to identify novel biomarkers to aid in the early detection and the accurate prediction of tumour behaviour. One group of proteins that is emerging as a potentially important group of markers in multiple tumour types is the S100 family. This review summarises the biological and clinical relevance of these proteins in relation to different tumour types.

Methods

A literature search was performed using the PubMed database and the reference lists of relevant articles. Single case studies were excluded and only reports with a clinical relevance from 1961 to 2007 were included.

Results

The search yielded over 1000 published articles and reports. Important reports and studies were reviewed, screened and tracked for further relevant publications. Only the most relevant publications are discussed with relation to individual members of the S100 family.

Conclusion

There is increasing evidence that altered expression of S100 family members is seen in many cancers including breast, lung, bladder, kidney, thyroid, gastric, prostate and oral cancers. S100 proteins are commonly up-regulated in tumours and this is often associated with tumour progression. In contrast S100A2, S100A11 and S100A9 have been documented as tumour suppressors in some cancers but as tumour promoters in others. This demonstrates the complexity of the family and variability of their functions. Although the precise roles of these proteins in cancer is still to be discovered many of the family are associated with promoting metastases through interactions with matrix metalloproteinases or by acting as chemoattractants. There is also evidence that some members can regulate transcription factors such as p53. S100B already has a role in a clinical setting in the diagnosis and therapeutic monitoring of malignant melanoma. As our understanding of this family develops it is likely that many more members will aid the diagnosis, monitoring and potential treatment of cancers in the future.

Introduction

The S100 proteins are a multi-gene calcium-binding family comprising 20 known human members each coded by a separate gene. At least 16 of these genes cluster to chromosome 1q21, known as the epidermal differentiation complex1, 2 (Table 1). The S100 proteins are small, acidic proteins of 10–12 kDa, found exclusively in vertebrates.³ The first member was identified in 1965 by Moore who christened a subcellular fraction from bovine brain “S100” because the constituents were soluble in 100% saturated ammonium sulphate at neutral pH.4, 5 Since then expression of S100 proteins has been demonstrated in a diverse spectrum of tissues. This paper summarizes the expression pattern of different members of the family in various solid tumours and discusses how detection may be useful for diagnosis, monitoring and as possible therapeutic targets.

The nomenclature of these proteins is very complex; each individual protein is known by several names, which can make processing the literature challenging. This has recently been simplified and the current nomenclature is summarised in Table 1.