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L ‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors
Author(s) -
Nawashiro Hiroshi,
Otani Naoki,
Shinomiya Nariyoshi,
Fukui Shinji,
Ooigawa Hidetoshi,
Shima Katsuji,
Matsuo Hirotaka,
Kanai Yoshikatsu,
Endou Hitoshi
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21866
Subject(s) - glioma , in vivo , immunohistochemistry , in vitro , biology , cancer research , transporter , amino acid , antigen , chemistry , microbiology and biotechnology , biochemistry , immunology , gene , genetics
L ‐type amino acid transporter 1 (LAT1) is a Na + ‐independent neutral amino acid transport agency and essential for the transport of large neutral amino acids. LAT1 has been identified as a light chain of the CD98 heterodimer from C6 glioma cells. LAT1 also corresponds to TA1, an oncofetal antigen that is expressed primarily in fetal tissues and cancer cells. We have investigated for the first time, the expression of the transporter in the human primary astrocytic tumor tissue from 60 patients. LAT1 is unique because it requires an additional single membrane spanning protein, the heavy chain of 4F2 cell surface antigen (4F2hc), for its functional expression. 4F2hc expression was also determined by immunohistochemistry. Kaplan‐Meier analyses demonstrated that high LAT1 expression correlated with poor survival for the study group as a whole ( p < 0.0001) and for those with glioblastoma multiforme in particular ( p = 0.0001). Cox regression analyses demonstrated that LAT1 expression was one of significant predictors of outcome, independent of all other variables. On the basis of these findings, we also investigated the effect of the specific inhibitor to LAT1, 2‐aminobicyclo‐2 (2,2,1)‐heptane‐2‐carboxylic acid (BCH), on the survival of C6 glioma cells in vitro and in vivo using a rat C6 glioma model. BCH inhibited the growth of C6 glioma cells in vitro and in vivo in a dose‐dependent manner. Kaplan‐Meier survival data of rats treated with BCH were significant. These findings suggest that LAT1 could be one of the molecular targets in glioma therapy. © 2006 Wiley‐Liss, Inc.