Fig. 4
Anti-angiogenic effects of LAT1 inhibition and endothelial-specific LAT1 depletion in in vivo tumor models. a Growth of MIA PaCa-2 xenograft tumors in athymic nude mice. White bar indicates the period of daily drug administration. Control, placebo treatment; JPH203, 25 mg/kg/day i.v. (n = 5 each). b Tissue weight and c gross appearance of xenograft tumors collected on Day 21. d Immunofluorescence of CD34 in the tumor paraffin sections. e Quantification of the density of CD34-positive intratumoral blood vessels. f Immunohistochemistry of LAT1 and CD34 in the paraffin sections of orthotopic syngeneic tumor model of B16-F10 cells in C57BL/6 J mice. LAT1 was stained with mLAT1 (c) antibody (LAT1(Ms)). Arrowheads indicate endothelial staining of LAT1. g Growth of B16-F10 tumors in Lat1fl/fl and Lat1fl/fl/Tek-Cre mice (n = 4 each). h Gross appearance of tumors collected on Day 10. i Intratumoral blood vessels visualized by intravenously injected FITC-Dextran. j Quantification of the blood vessel area on tumor sections