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Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells

Despite overall progress in improving cancer treatments, the complete response of mantle cell lymphoma (MCL) is still limited due to the inevitable development of drug resistance. More than half of patients did not attain response to bortezomib (BTZ), the approved treatment for relapsed or refractor...

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Autores principales: Luanpitpong, Sudjit, Janan, Montira, Thumanu, Kanjana, Poohadsuan, Jirarat, Rodboon, Napachai, Klaihmon, Phatchanat, Issaragrisil, Surapol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521097/
https://www.ncbi.nlm.nih.gov/pubmed/31022903
http://dx.doi.org/10.3390/cancers11040576
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author Luanpitpong, Sudjit
Janan, Montira
Thumanu, Kanjana
Poohadsuan, Jirarat
Rodboon, Napachai
Klaihmon, Phatchanat
Issaragrisil, Surapol
author_facet Luanpitpong, Sudjit
Janan, Montira
Thumanu, Kanjana
Poohadsuan, Jirarat
Rodboon, Napachai
Klaihmon, Phatchanat
Issaragrisil, Surapol
author_sort Luanpitpong, Sudjit
collection PubMed
description Despite overall progress in improving cancer treatments, the complete response of mantle cell lymphoma (MCL) is still limited due to the inevitable development of drug resistance. More than half of patients did not attain response to bortezomib (BTZ), the approved treatment for relapsed or refractory MCL. Understanding how MCL cells acquire BTZ resistance at the molecular level may be a key to the long-term management of MCL patients and new therapeutic strategies. We established a series of de novo BTZ-resistant human MCL-derived cells with approximately 15- to 60-fold less sensitivity than those of parental cells. Using gene expression profiling, we discovered that putative cancer-related genes involved in drug resistance and cell survival tested were mostly downregulated, likely due to global DNA hypermethylation. Significant information on dysregulated lipid metabolism was obtained from synchrotron-based Fourier transform infrared (FTIR) spectroscopy of single cells. We demonstrated for the first time an upregulation of CD36 in highly BTZ-resistant cells in accordance with an increase in their lipid accumulation. Ectopic expression of CD36 causes an increase in lipid droplets and renders BTZ resistance to various human MCL cells. By contrast, inhibition of CD36 by neutralizing antibody strongly enhances BTZ sensitivity, particularly in CD36-overexpressing cells and de novo BTZ-resistant cells. Together, our findings highlight the potential application of CD36 inhibition for BTZ sensitization and suggest the use of FTIR spectroscopy as a promising technique in cancer research.
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spelling pubmed-65210972019-05-31 Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells Luanpitpong, Sudjit Janan, Montira Thumanu, Kanjana Poohadsuan, Jirarat Rodboon, Napachai Klaihmon, Phatchanat Issaragrisil, Surapol Cancers (Basel) Article Despite overall progress in improving cancer treatments, the complete response of mantle cell lymphoma (MCL) is still limited due to the inevitable development of drug resistance. More than half of patients did not attain response to bortezomib (BTZ), the approved treatment for relapsed or refractory MCL. Understanding how MCL cells acquire BTZ resistance at the molecular level may be a key to the long-term management of MCL patients and new therapeutic strategies. We established a series of de novo BTZ-resistant human MCL-derived cells with approximately 15- to 60-fold less sensitivity than those of parental cells. Using gene expression profiling, we discovered that putative cancer-related genes involved in drug resistance and cell survival tested were mostly downregulated, likely due to global DNA hypermethylation. Significant information on dysregulated lipid metabolism was obtained from synchrotron-based Fourier transform infrared (FTIR) spectroscopy of single cells. We demonstrated for the first time an upregulation of CD36 in highly BTZ-resistant cells in accordance with an increase in their lipid accumulation. Ectopic expression of CD36 causes an increase in lipid droplets and renders BTZ resistance to various human MCL cells. By contrast, inhibition of CD36 by neutralizing antibody strongly enhances BTZ sensitivity, particularly in CD36-overexpressing cells and de novo BTZ-resistant cells. Together, our findings highlight the potential application of CD36 inhibition for BTZ sensitization and suggest the use of FTIR spectroscopy as a promising technique in cancer research. MDPI 2019-04-24 /pmc/articles/PMC6521097/ /pubmed/31022903 http://dx.doi.org/10.3390/cancers11040576 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luanpitpong, Sudjit
Janan, Montira
Thumanu, Kanjana
Poohadsuan, Jirarat
Rodboon, Napachai
Klaihmon, Phatchanat
Issaragrisil, Surapol
Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
title Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
title_full Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
title_fullStr Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
title_full_unstemmed Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
title_short Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells
title_sort deciphering the elevated lipid via cd36 in mantle cell lymphoma with bortezomib resistance using synchrotron-based fourier transform infrared spectroscopy of single cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521097/
https://www.ncbi.nlm.nih.gov/pubmed/31022903
http://dx.doi.org/10.3390/cancers11040576
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