This finding is consistent with many reports showing that S1P is produced intracellularly by SphK1 and exerts its paracrine/autocrine effects by being secreted into the tumor microenvironment.48 Spinster 2 (Spns2) is believed to be the primary transporter in the release of S1P.6 Thus, when CAKI-1 and A498 cells were treated with Spns2-specific siRNAs, the expression of Spns2 protein decreased to less than 20–30% of the control with two different siRNAs (Figure 6b). The gene discussed is SPHK1; the disease is neoplasm.