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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

1
Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
2
Synchrotron Light Research Institute (Public Organization), Nakhon Ratchasima 30000, Thailand
3
Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
4
Bangkok Hematology Center, Wattanosoth Hospital, BDMS Center of Excellence for Cancer, Bangkok 10310, Thailand
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 576; https://doi.org/10.3390/cancers11040576
Received: 18 February 2019 / Revised: 6 April 2019 / Accepted: 22 April 2019 / Published: 24 April 2019
(This article belongs to the Special Issue Metabolic Reprogramming and Vulnerabilities in Cancer)
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Abstract

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. View Full-Text
Keywords: mantle cell lymphoma; bortezomib resistance; lipid metabolism; CD36; fourier transform infrared spectroscopy; single cells mantle cell lymphoma; bortezomib resistance; lipid metabolism; CD36; fourier transform infrared spectroscopy; single cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Luanpitpong, S.; Janan, M.; Thumanu, K.; Poohadsuan, J.; Rodboon, N.; Klaihmon, P.; Issaragrisil, S. Deciphering the Elevated Lipid via CD36 in Mantle Cell Lymphoma with Bortezomib Resistance Using Synchrotron-Based Fourier Transform Infrared Spectroscopy of Single Cells. Cancers 2019, 11, 576.

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