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Open Access Research article

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

Zhen Haining12, Nobuyuki Kawai1*, Keisuke Miyake1, Masaki Okada1, Shuichi Okubo1, Xiang Zhang2*, Zhou Fei2* and Takashi Tamiya1

Author Affiliations

1 Department of Neurological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

2 Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032 China

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BMC Clinical Pathology 2012, 12:4  doi:10.1186/1472-6890-12-4

Published: 28 February 2012

Abstract

Background

LAT1/4F2hc heterodimeric complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Although it has been shown that LAT1/4F2hc is highly expressed in a variety of human tumors including gliomas, and LAT1 over-expression is associated with glioma grade and poor prognosis of glioma patients, the precise tissue location of LAT1/4F2hc in gliomas and the precise role of LAT1/4F2hc in glioma biological features remain unclear.

Methods

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.

Results

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.

Conclusion

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.