Fig. 1
From: Mouse genomic screen reveals novel host regulator of metastasis
Endothelial SPNS2 regulates lymphocyte trafficking to influence metastatic colonization. After extravasation into the lung parenchyma following dissemination through vascular or lymphatic systems, cancer cells normally encounter a hostile environment dominated by immune defenses. In wild-type mice (left panel), the S1P transporter SPNS2 regulates the circulation levels of S1P and maintains lymphocyte trafficking homeostasis as well as organ regulatory T (T reg ) cells. In this scenario, the Treg cells are abundant in the lung tissue, which facilitates the colonization of highly metastatic tumor cells. However, in the Spns2-deficient mice (Spns2 tm1a/tm1a; right panel), S1P levels are decreased in circulation but are higher in the lungs, disrupting lymphocyte trafficking. This results in an increased ratio of cytotoxic CD8+ T cells and natural killer (NK) cells in the lungs, which prevents metastatic colonization of arriving cancer cells