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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer

Authors: Kyoichi Kaira, Yutaka Sunose, Yasuhiro Ohshima, Noriko S Ishioka, Kazuhisa Arakawa, Tetsushi Ogawa, Noriaki Sunaga, Kimihiro Shimizu, Hideyuki Tominaga, Noboru Oriuchi, Hideaki Itoh, Shushi Nagamori, Yoshikatsu Kanai, Aiko Yamaguchi, Atsuki Segawa, Munenori Ide, Masatomo Mori, Tetsunari Oyama, Izumi Takeyoshi

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor cell growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine biological significance of LAT1 expression and investigate whether LAT1 could be a prognostic biomarker for biliary tract cancer.

Methods

A total of 139 consecutive patients with resected pathologic stage I-IV biliary tract adenocarcinoma were retrospectively reviewed. Tumor specimens were stained by immunohistochemistry for LAT1, Ki-67, microvessel density determined by CD34, and p53; and prognosis of patients was correlated. Biological significance of LAT1 expression was investigated by in vitro and in vivo experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using cholangiocarcinoma cell line.

Results

In total patients, high LAT1 expressions were recognized in 64.0%. The expression of LAT1 was closely correlated with lymphatic metastases, cell proliferation and angiogenesis, and was a significant indicator for predicting poor outcome after surgery. LAT1 expression was a significant independent predictor by multivariate analysis. Both in vitro and in vivo preliminary experiments indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to gemcitabine and 5-FU.

Conclusions

High expression of LAT1 is a promising pathological marker to predict the outcome in patients with biliary tract adenocarcinoma. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.
Appendix
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Metadata
Title
Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer
Authors
Kyoichi Kaira
Yutaka Sunose
Yasuhiro Ohshima
Noriko S Ishioka
Kazuhisa Arakawa
Tetsushi Ogawa
Noriaki Sunaga
Kimihiro Shimizu
Hideyuki Tominaga
Noboru Oriuchi
Hideaki Itoh
Shushi Nagamori
Yoshikatsu Kanai
Aiko Yamaguchi
Atsuki Segawa
Munenori Ide
Masatomo Mori
Tetsunari Oyama
Izumi Takeyoshi
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-482

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