Importantly, in vivo xenograft experiments suggested that growth and M2 macrophage polarization, but not total infiltration, were compromised in mice injected with MCF-7 breast cancer cells carrying a short hairpin (sh)RNA plasmid to downregulate SphK2, strongly suggesting a role for this isoform in S1P-mediated macrophage growth and M2 polarization (114). This evidence concerns the gene SPHK2 and breast carcinoma.