Expression of large neutral amino acid transporters LAT1 and LAT2 in medulloblastoma

Na+-independent large neutral amino acid transporters (LATs) represent the main intracellular transport route for several essential amino acids, such as leucine, isoleucine, valine, phenylalanine, tryptophan and methionine. Four LATs (LAT 1–4) have been identified so far; of those, LAT1 is the most extensively studied because of its limited distribution in normal organs and tissues, and high expression in a number of tumor types [1]. In astrocytic tumors, LAT1 overexpression represents a negative prognostic marker that has been linked to tumor grade, proliferating potential and angiogenesis [2, 3, 4]. Blocking of Na+-independent large neutral amino acid transporters using 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) produced significant cell killing in vitro, and prolonged survival in an orthotopic glioma rat model [3]. LAT1 mediates the intracellular transport of several anticancer compounds, such as melphalan, acivicin and fenclonine, and is the target of specific inhibitors that have promise in preclinical models of human cancers