ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer

被引:103
作者
Shimizu, K. [1 ]
Kaira, K. [2 ,3 ]
Tomizawa, Y. [4 ]
Sunaga, N. [2 ]
Kawashima, O. [5 ]
Oriuchi, N. [6 ]
Tominaga, H. [7 ]
Nagamori, S. [8 ]
Kanai, Y. [8 ]
Yamada, M. [2 ]
Oyama, T. [3 ]
Takeyoshi, I. [1 ]
机构
[1] Gunma Univ, Grad Sch Med, Dept Thorac & Visceral Surg, Maebashi, Gunma 3718511, Japan
[2] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Maebashi, Gunma 371, Japan
[3] Gunma Univ, Grad Sch Med, Dept Diagnost Pathol, Maebashi, Gunma 371, Japan
[4] NHO Nishi Gunma Hosp, Dept Internal Med, Gunma, Japan
[5] NHO Nishi Gunma Hosp, Dept Surg, Gunma, Japan
[6] Gunma Univ, Grad Sch Med, Dept Diagnost Radiol & Nucl Med, Maebashi, Gunma 371, Japan
[7] Gunma Univ, Grad Sch Med, Dept Mol Imaging, Maebashi, Gunma 371, Japan
[8] Osaka Univ, Grad Sch Med, Dept Pharmacol, Div Biosyst Pharmacol, Osaka, Japan
关键词
ASCT2; non-small cell lung cancer; amino-acid transporter; prognostic factor; HIGH EXPRESSION; LAT1; INHIBITION; HISTOLOGY; SURVIVAL; CLONING; GENDER; TARGET; GROWTH;
D O I
10.1038/bjc.2014.88
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear. Methods: One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort. Results: ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients. Conclusions: ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery.
引用
收藏
页码:2030 / 2039
页数:10
相关论文
共 27 条
[1]   ANTIBODIES OF PREDETERMINED SPECIFICITY AGAINST CHEMICALLY SYNTHESIZED PEPTIDES OF HUMAN INTERLEUKIN-2 [J].
ALTMAN, A ;
CARDENAS, JM ;
HOUGHTEN, RA ;
DIXON, FJ ;
THEOFILOPOULOS, AN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (07) :2176-2180
[2]   Prognostic factors in non-small cell lung cancer - A decade of progress [J].
Brundage, MD ;
Davies, D ;
Mackillop, WJ .
CHEST, 2002, 122 (03) :1037-1057
[3]   Identification and characterization of a novel member of the heterodimeric amino acid transporter family presumed to be associated with an unknown heavy chain [J].
Chairoungdua, A ;
Kanai, Y ;
Matsuo, H ;
Inatomi, J ;
Kim, DK ;
Endou, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (52) :49390-49399
[4]   Amino acid transporters ASCT2 and LAT1 in cancer: Partners in crime? [J].
Fuchs, BC ;
Bode, BP .
SEMINARS IN CANCER BIOLOGY, 2005, 15 (04) :254-266
[5]   ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells [J].
Fuchs, Bryan C. ;
Finger, Richard E. ;
Onan, Marie C. ;
Bode, Barrie P. .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2007, 293 (01) :C55-C63
[6]   Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis [J].
Furuya, Mio ;
Horiguchi, Jun ;
Nakajima, Hiroki ;
Kanai, Yoshikatsu ;
Oyama, Tetsunari .
CANCER SCIENCE, 2012, 103 (02) :382-389
[7]   High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: Comparison with non-cancerous lesions [J].
Ichinoe, Masaaki ;
Mikami, Tetuo ;
Yoshida, Tsutomu ;
Igawa, Ikuyo ;
Tsuruta, Tomoko ;
Nakada, Norihiro ;
Anzai, Naohiko ;
Suzuki, Yoshiyuki ;
Endou, Hitoshi ;
Okayasu, Isao .
PATHOLOGY INTERNATIONAL, 2011, 61 (05) :281-289
[8]  
Imai H, 2010, ANTICANCER RES, V30, P4819
[9]   Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer [J].
Kaira, K. ;
Oriuchi, N. ;
Imai, H. ;
Shimizu, K. ;
Yanagitani, N. ;
Sunaga, N. ;
Hisada, T. ;
Tanaka, S. ;
Ishizuka, T. ;
Kanai, Y. ;
Endou, H. ;
Nakajima, T. ;
Mori, M. .
BRITISH JOURNAL OF CANCER, 2008, 98 (04) :742-748
[10]   Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer [J].
Kaira, K. ;
Sunose, Y. ;
Arakawa, K. ;
Ogawa, T. ;
Sunaga, N. ;
Shimizu, K. ;
Tominaga, H. ;
Oriuchi, N. ;
Itoh, H. ;
Nagamori, S. ;
Kanai, Y. ;
Segawa, A. ;
Furuya, M. ;
Mori, M. ;
Oyama, T. ;
Takeyoshi, I. .
BRITISH JOURNAL OF CANCER, 2012, 107 (04) :632-638