Sphingosine-1-phosphate (S1P) in cancer immunity and development

Sphingosine-1-phosphate (S1P) is a cellular and extracellular signaling molecule that acts locally in different organs and is also systemically present in blood and lymph. S1P is a well characterized immune modulator influencing lymphocyte circulation and immune cell differentiation, survival, function, migration, and locality. Many of these functions are also relevant for the pathology of tumor cells, and there is a body of evidence supporting the fact that S1P fulfils similar functions in cancer. This review aims to summarize the current knowledge about the roles of S1P in tumor growth and survival, cancer cell invasion and metastasis, and cancer development and neoplasia. Different mechanistic concepts are discussed, including S1P receptor and inside-out signaling, adaptation, immune escape mechanisms, and the sphingolipid rheostat.