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Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth

PURPOSE: Glutamine (Gln) is essential for the proliferation of most cancer cells, making it an appealing target for cancer therapy. However, the role of Gln in gastric cancer (GC) metabolism is unknown and Gln-targeted therapy against GC remains scarce. The aim of this study was to investigate the r...

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Autores principales: Ye, Jianxin, Huang, Qiang, Xu, Jie, Huang, Jinsheng, Wang, Jinzhou, Zhong, Wenjing, Chen, Wannan, Lin, Xinjian, Lin, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916984/
https://www.ncbi.nlm.nih.gov/pubmed/29435734
http://dx.doi.org/10.1007/s00432-018-2605-9
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author Ye, Jianxin
Huang, Qiang
Xu, Jie
Huang, Jinsheng
Wang, Jinzhou
Zhong, Wenjing
Chen, Wannan
Lin, Xinjian
Lin, Xu
author_facet Ye, Jianxin
Huang, Qiang
Xu, Jie
Huang, Jinsheng
Wang, Jinzhou
Zhong, Wenjing
Chen, Wannan
Lin, Xinjian
Lin, Xu
author_sort Ye, Jianxin
collection PubMed
description PURPOSE: Glutamine (Gln) is essential for the proliferation of most cancer cells, making it an appealing target for cancer therapy. However, the role of Gln in gastric cancer (GC) metabolism is unknown and Gln-targeted therapy against GC remains scarce. The aim of this study was to investigate the relevance of Gln in GC growth and targeting. METHODS: Expression of Gln transporter ASCT2 and glutamine synthetase (GS) in the parental and molecularly engineered GC cells or in human GC specimens was determined by RT-PCR and western blot analysis or immunohistochemistry. Cell proliferation and survival was assessed by CCK-8 assay and colony formation assay. Intracellular Gln content was measured by a HPLC system. Effects of ASCT2 and/or GS inhibitor on tumor growth were investigated in xenograft models. RESULTS: A significant heterogeneity of GC cells was observed with respect to their response to the treatment of ASCT2 inhibitor benzylserine (BenSer). Gln deprivation did not affect the BenSer-resistant cell growth due to endogenous GS expression, whose inhibition remarkably reduced cell proliferation. The differential in vitro sensitivity correlated with overall intracellular Gln content. Combined therapy with both ASCT2 and GS inhibitors produced a greater therapeutic efficacy than the treatment of either inhibitor alone. Furthermore, 77% human GC tissues were found to express moderate and high levels of ASCT2, 12% of which also co-expressed relatively high levels of GS. CONCLUSION: Gln mediates GC growth and the therapeutic efficacy of Gln-targeted treatment relies on distinct ASCT2 and GS expression pattern in specific gastric cancer groups.
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spelling pubmed-59169842018-04-30 Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth Ye, Jianxin Huang, Qiang Xu, Jie Huang, Jinsheng Wang, Jinzhou Zhong, Wenjing Chen, Wannan Lin, Xinjian Lin, Xu J Cancer Res Clin Oncol Original Article – Cancer Research PURPOSE: Glutamine (Gln) is essential for the proliferation of most cancer cells, making it an appealing target for cancer therapy. However, the role of Gln in gastric cancer (GC) metabolism is unknown and Gln-targeted therapy against GC remains scarce. The aim of this study was to investigate the relevance of Gln in GC growth and targeting. METHODS: Expression of Gln transporter ASCT2 and glutamine synthetase (GS) in the parental and molecularly engineered GC cells or in human GC specimens was determined by RT-PCR and western blot analysis or immunohistochemistry. Cell proliferation and survival was assessed by CCK-8 assay and colony formation assay. Intracellular Gln content was measured by a HPLC system. Effects of ASCT2 and/or GS inhibitor on tumor growth were investigated in xenograft models. RESULTS: A significant heterogeneity of GC cells was observed with respect to their response to the treatment of ASCT2 inhibitor benzylserine (BenSer). Gln deprivation did not affect the BenSer-resistant cell growth due to endogenous GS expression, whose inhibition remarkably reduced cell proliferation. The differential in vitro sensitivity correlated with overall intracellular Gln content. Combined therapy with both ASCT2 and GS inhibitors produced a greater therapeutic efficacy than the treatment of either inhibitor alone. Furthermore, 77% human GC tissues were found to express moderate and high levels of ASCT2, 12% of which also co-expressed relatively high levels of GS. CONCLUSION: Gln mediates GC growth and the therapeutic efficacy of Gln-targeted treatment relies on distinct ASCT2 and GS expression pattern in specific gastric cancer groups. Springer Berlin Heidelberg 2018-02-12 2018 /pmc/articles/PMC5916984/ /pubmed/29435734 http://dx.doi.org/10.1007/s00432-018-2605-9 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article – Cancer Research
Ye, Jianxin
Huang, Qiang
Xu, Jie
Huang, Jinsheng
Wang, Jinzhou
Zhong, Wenjing
Chen, Wannan
Lin, Xinjian
Lin, Xu
Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth
title Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth
title_full Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth
title_fullStr Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth
title_full_unstemmed Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth
title_short Targeting of glutamine transporter ASCT2 and glutamine synthetase suppresses gastric cancer cell growth
title_sort targeting of glutamine transporter asct2 and glutamine synthetase suppresses gastric cancer cell growth
topic Original Article – Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916984/
https://www.ncbi.nlm.nih.gov/pubmed/29435734
http://dx.doi.org/10.1007/s00432-018-2605-9
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