Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
Curr Opin Pharmacol. 2013 Aug;13(4):588-94. doi: 10.1016/j.coph.2013.04.007. Epub 2013 May 9.
The S100 protein family is involved in epithelial cell maturation and inflammation. Some S100 members are dysregulated during carcinogenesis and have been established as tumor markers. Psoriasin (S100A7) and koebnerisin (S100A15) are highly homologous proteins that have been first described in psoriasis, which is characterized by disturbed epidermal maturation and chronic inflammation. Despite their homology, both S100 proteins are distinct in expression and function through different receptors but synergize as chemoattractants and pro-inflammatory 'alarmins' to promote inflammation. Psoriasin and koebnerisin are further regulated with tumor progression in epithelial cancers. In tumor cells, high cytoplasmic expression of psoriasin and koebnerisin may prevent oncogenic activity, whereas their nuclear translocation and extracellular secretion are associated with tumor progression and poor prognosis. The present review outlines these opposing effects of psoriasin and koebnerisin in multifunctional pathways and mechanisms that are known to affect tumor cells ('seeds'), tumor environment ('soil') and tumor cell metastasis ('seeding') thereby influencing epithelial carcinogenesis.
S100 蛋白家族参与上皮细胞成熟和炎症。一些 S100 成员在癌变过程中失调，并已被确立为肿瘤标志物。Psoriasin（S100A7）和 koebnerisin（S100A15）是高度同源的蛋白质，最初在银屑病中描述，其特征是表皮成熟和慢性炎症紊乱。尽管它们具有同源性，但通过不同的受体，这两种 S100 蛋白在表达和功能上是不同的，但作为趋化因子和促炎“警报素”协同作用，促进炎症。Psoriasin 和 koebnerisin 还通过上皮癌的肿瘤进展进一步受到调节。在肿瘤细胞中，高细胞质表达 psoriasin 和 koebnerisin 可能阻止致癌活性，而其核转位和细胞外分泌与肿瘤进展和预后不良相关。本综述概述了 psoriasin 和 koebnerisin 在已知影响肿瘤细胞（“种子”）、肿瘤环境（“土壤”）和肿瘤细胞转移（“播种”）的多功能途径和机制中的这些相反作用，从而影响上皮癌的发生。
