In another similar in vitro study, however, lymphatic malformation-derived LECs were highly susceptible to treatment with the mTOR pathway inhibitor sirolimus, but not VEGFR3 blockade, initially suggesting upstream VEGFC-VEGFR3 signaling does not play a significant role in the development of hyperproliferative phenotypes in lymphatic malformations (Osborn et al., 2015). This evidence concerns the gene VEGFC and lymphatic malformation.