Fig. 5: Co-inhibition of the upstream VEGF-C/VEGFR3 and the downstream mTOR signaling pathways promotes LM regression.
From: Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation
a Experimental plan for the induction and treatment of progressive microcystic LM using a combination therapy with VEGF-C trap and Rapamycin. b Whole-mount staining of ears from PIK3CAH1047R;Vegfr3-CreERT2 control (Ctrl) and 4-OHT-treated (100 µg) mice at 5 weeks of age, or following a 1.5-week treatment with Rapamycin, AAV-sR3 and/or vehicles at 6.5 weeks of age. c Quantification of lymphatic vessel branching in the PIK3CAH1047R;Vegfr3-CreERT2 mice. Stages of analysis and treatments are indicated. Data represent mean (n = number of ears as indicated) ± s.e.m. d Flow cytometry analysis of dermal LEC proliferation in the PIK3CAH1047R;Vegfr3-CreERT2 mice treated as indicated. Data represent mean (n = number of mice as indicated) ± s.d. e Lymphatic vessel morphology in areas of hypersprouting in 6.5-week-old 4-OHT-treated PIK3CAH1047R;Vegfr3-CreERT2 ears. Note blunt morphology of lymphatic sprouts in mice treated with Rapamycin and AAV-sR3 compared with vehicle-treated mice (yellow arrows). f Quantification of all vessel ends and their morphology (upper graph), with data shown separately for spiky ends representing active sprouts (lower graph), in the indicated groups. Data represent mean (n = number of mice as indicated ± s.e.m.) Two-tailed unpaired Student’s t-test. Scale bars: 200 µm (b), 100 µm (e). Source data are provided as a Source Data file.
