Article

L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors

Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
International Journal of Cancer (Impact Factor: 5.01). 08/2006; 119(3):484-92. DOI: 10.1002/ijc.21866
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ABSTRACT 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.

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Available from: Hiroshi Nawashiro, Apr 03, 2015
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    • "Recent studies have focussed on ASCT2 and LAT1, which are highly expressed in cancer cells (Fuchs and Bode, 2006). The overexpression of LAT1 may be a significant predictor of poor prognosis, and it is closely linked to the aggressiveness and metastasis of various human neoplasms (Nawashiro et al, 2006; Nakanishi et al, 2007; Kaira et al, 2008, 2012; Sakata et al, 2009; Ichinoe et al, 2011; Furuya et al; 2012). "
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    • "only for protein synthesis but also for the stimulation of cancer cell growth via mammalian targeting of rapamycin (Fuchs and Bode, 2006). Although LAT1 has been described to have a crucial role in the pathogenesis of human neoplasms, the clinical significance of LAT1 expression in pancreatic cancer remains unclear (Fuchs and Bode, 2006; Nawashiro et al, 2006; Nakanishi et al, 2007; Kaira et al, 2008; Sakata et al, 2009; Ichinoe et al, 2011). Previous studies have demonstrated that LAT1 expression is closely associated with CD98, cell proliferation (Ki-67-labelling index), the cell cycle regulator p53 and angiogenesis in patients with thoracic tumours (Kaira et al, 2011a, 2011b). "
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