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Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells
BACKGROUND: Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which fa...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396336/ https://www.ncbi.nlm.nih.gov/pubmed/22700320 http://dx.doi.org/10.1007/s13402-012-0081-9 |
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author | Cheng, Chang Edin, Nina F. Jeppesen Lauritzen, Knut H. Aspmodal, Ida Christoffersen, Stine Jian, Liu Rasmussen, Lene Juel Pettersen, Erik O Xiaoqun, Gao Bergersen, Linda H. |
author_facet | Cheng, Chang Edin, Nina F. Jeppesen Lauritzen, Knut H. Aspmodal, Ida Christoffersen, Stine Jian, Liu Rasmussen, Lene Juel Pettersen, Erik O Xiaoqun, Gao Bergersen, Linda H. |
author_sort | Cheng, Chang |
collection | PubMed |
description | BACKGROUND: Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma. MATERIAL AND METHODS: In order to identify differences in the capacity for lactate exchange, human T-47D breast cancer cells and human glioblastoma T98G cells were grown under 4 % or 20 % oxygen conditions and examined for MCT1, MCT2 and MCT4 expression on plasma membranes by quantitative post embedding immunogold electron microscopy. Whereas previous studies on MCT expression in tumours have recorded mRNA and protein levels in cell extracts, we examined concentrations of the proteins in the microvillous plasma membrane protrusions specialized for transmembrane transport. RESULTS: In normoxia, both tumour cell types highly expressed the low affinity transporter MCT4, which is thought to mainly mediate monocarboxylate efflux, while for high affinity transport the breast tumour cells preferentially expressed MCT1 and the brain tumour cells resembled brain neurons in expressing MCT2, rather than MCT1. The expressions of MCT1 and MCT4 were upregulated in hypoxic conditions in both breast and brain tumour cells. The expression of MCT2 also increased in hypoxic breast cancer cells, but decreased in hypoxic brain tumour cells. Quantitative immunoblots showed similar hypoxia induced changes in the protein levels. CONCLUSION: The differential expression and regulation of MCTs in the surface membranes of hypoxic and normoxic tumour cells of different types provide a foundation for innovation in tumour therapy through the selective targeting of MCTs. Selective inhibition of various MCTs could be an efficient way to quench an important energy source in both original breast tumour and metastatic cancer tissue in the brain. |
format | Online Article Text |
id | pubmed-3396336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-33963362012-07-17 Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells Cheng, Chang Edin, Nina F. Jeppesen Lauritzen, Knut H. Aspmodal, Ida Christoffersen, Stine Jian, Liu Rasmussen, Lene Juel Pettersen, Erik O Xiaoqun, Gao Bergersen, Linda H. Cell Oncol (Dordr) Original Paper BACKGROUND: Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma. MATERIAL AND METHODS: In order to identify differences in the capacity for lactate exchange, human T-47D breast cancer cells and human glioblastoma T98G cells were grown under 4 % or 20 % oxygen conditions and examined for MCT1, MCT2 and MCT4 expression on plasma membranes by quantitative post embedding immunogold electron microscopy. Whereas previous studies on MCT expression in tumours have recorded mRNA and protein levels in cell extracts, we examined concentrations of the proteins in the microvillous plasma membrane protrusions specialized for transmembrane transport. RESULTS: In normoxia, both tumour cell types highly expressed the low affinity transporter MCT4, which is thought to mainly mediate monocarboxylate efflux, while for high affinity transport the breast tumour cells preferentially expressed MCT1 and the brain tumour cells resembled brain neurons in expressing MCT2, rather than MCT1. The expressions of MCT1 and MCT4 were upregulated in hypoxic conditions in both breast and brain tumour cells. The expression of MCT2 also increased in hypoxic breast cancer cells, but decreased in hypoxic brain tumour cells. Quantitative immunoblots showed similar hypoxia induced changes in the protein levels. CONCLUSION: The differential expression and regulation of MCTs in the surface membranes of hypoxic and normoxic tumour cells of different types provide a foundation for innovation in tumour therapy through the selective targeting of MCTs. Selective inhibition of various MCTs could be an efficient way to quench an important energy source in both original breast tumour and metastatic cancer tissue in the brain. Springer Netherlands 2012-06-15 2012 /pmc/articles/PMC3396336/ /pubmed/22700320 http://dx.doi.org/10.1007/s13402-012-0081-9 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Paper Cheng, Chang Edin, Nina F. Jeppesen Lauritzen, Knut H. Aspmodal, Ida Christoffersen, Stine Jian, Liu Rasmussen, Lene Juel Pettersen, Erik O Xiaoqun, Gao Bergersen, Linda H. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
title | Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
title_full | Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
title_fullStr | Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
title_full_unstemmed | Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
title_short | Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
title_sort | alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396336/ https://www.ncbi.nlm.nih.gov/pubmed/22700320 http://dx.doi.org/10.1007/s13402-012-0081-9 |
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