Molecular Characterization of Amino Acid Transporter System L Involved in Borophenylalanine Uptake for BNCT in Melanoma

ROSSINI, A E; THOMASZ, L; DAGROSA, MA; CARPANO, M; JUVENAL, GJ; PISAREV , M

Buenos Aires

Congreso; 14th International Congress of Neutron Capture Therapy; 2010

CNEA, UNSAM, ROFFO

 It´s well known that the effectiveness of the BNC therapy is directly related to the selective uptake of the boron carrier by tumor cells. In many cases the boron-linked molecule used is p-borophenylalanine (BPA), whose uptake is carried out predominantly by the large neutral amino acid transport system L, a dimeric amino acid exchanger anchored to the cell membrane and composed by two subunits: light chain LAT and heavy chain (hc) 4F2 / CD98. In an attempt to find out the molecular subunits involved in this intracellular uptake we have studied the expression profile of the four isoforms described of the light subunit component LAT, the catalytic subunit of the large neutral amino acid transporter. These profiles were studied using RT-PCR / standard PCR analysis of mRNA expression in five human melanoma cell lines: M8, Mel-J, A375, M1/15 and NPA demostrating coexpression of the different subunits in three of the five cell lines. Incubation in presence or absence of a specific System L competitive inhibitor,  aminobicyclo heptane carboxylic acid (BCH),  allowed to determine an important role of this transport system in the uptake of BPA by melanoma cell lines.