CD13/APN rescues capillary morphogenesis despite MEK or PI-3K inhibition.

(A) CD13/APN is required for capillary morphogenesis. HUVECs were plated on Matrigel containing the indicated CD13/APN functional antagonists or isotype-matched control antibody (control) and photographed after 18 to 24 hours. (B) Increased cell surface CD13/APN can rescue inhibited morphogenesis. EOMA engineered to express high levels of CD13/APN (20-fold increase, EOMA-CD13, bottom row) or vector control cells (EOMA-pcDNA, top row) were plated on Matrigel in the presence of the indicated Ras, MEK, or PI-3K inhibitors. (C) Transmembrane expression of CD13/APN is not required for rescue. HUVECs were plated on Matrigel containing microsomal membrane preparations of CD13-high cells (+ CD13, right column) or vector control cells (left column) in the absence (top row) or presence of the MEK inhibitor PD98059 (middle row) or both PD98059 and the aminopeptidase inhibitor bestatin (bottom row). Original magnification A-C, × 10.