Relation of LAT1/4F2hc expression with pathological grade, proliferation and angiogenesis in human gliomas

In the current study, the expressions of LAT1, 4F2hc, CD34 and Ki-67 were investigated by immunohistochemistry in 62 cases of human brain glioma; LAT1/4F2hc expression level, Ki-67 labeling index (Ki-67 LI) and microvessel density (MVD) were measured semi-quantitatively; and the correlation of LAT1/4F2hc expression with histopathological features, Ki-67 LI and MVD in gliomas was further analyzed.The results showed that both LAT1 and 4F2hc were expressed in all examined specimens. LAT1 but 4F2hc expression levels significantly correlated with the pathological grade and both expression levels significantly correlated with Ki-67 LI of gliomas. We also demonstrated that both LAT1 and 4F2hc immunoreactivity were observed in tumor cells as well as vascular endothelia; furthermore, the LAT1 expression level was markedly associated with glioma MVD as well.LAT1/4F2hc over-expression is closely correlates with the malignant phenotype and proliferation of gliomas, and LAT1 was associates with glioma angiogenesis. LAT1/4F2hc, especially LAT1, may become a novel potential molecular target for glioma biological therapy.In malignant tumor cells, a steady and sufficient sugar and amino acid supply is necessary to maintain a high degree of energy metabolism and protein synthesis for rapid growth and continuous proliferation, and such a supply is supported by the up-regulation of transporters specialized for those nutrients [1]. In terms of glucose supply, the over-expression of glucose transporter-1 (Glut-1) is related to increased glucose uptake in human tumors [1]. Transporters for essential amino acids are particularly important because they are indispensable for protein synthesis to maintain cell integrity and cell cycle progression. Among several amino acid transporters, system L, a Na+-independent amino acid transport system, is a major route for providing cells with large neutral amino acids, including branched or aromatic amino acids, which contain most of the essential amin