Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells

It is now admitted that in addition to acquired resistance, the tumor microenvironment contributes to the development of chemo-resistance and malignant progression. In a previous study, we showed that Dox induced apoptosis in FTC-133 cells by trigging JNK pathway. This process was accompanied by a d...

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Main Authors: Marie-Pierre Courageot, Laurent Duca, Laurent Martiny, Emmanuelle Devarenne-Charpentier, Hamid Morjani, Hassan El Btaouri
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2020.551228/full
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spelling doaj-0dd37bb5d3c5423f84547056f37a1b3f2020-12-08T08:33:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.551228551228Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 CellsMarie-Pierre Courageot0Laurent Duca1Laurent Martiny2Emmanuelle Devarenne-Charpentier3Hamid Morjani4Hassan El Btaouri5Laboratoire de Biospectroscopie Translationnelle (BioSpecT), UFR Pharmacie, Université de Reims Champagne Ardenne, Reims, FranceUMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, Reims, FranceUMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, Reims, FranceUMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, Reims, FranceLaboratoire de Biospectroscopie Translationnelle (BioSpecT), UFR Pharmacie, Université de Reims Champagne Ardenne, Reims, FranceUMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne Ardenne, Moulin de la Housse, Reims, FranceIt is now admitted that in addition to acquired resistance, the tumor microenvironment contributes to the development of chemo-resistance and malignant progression. In a previous study, we showed that Dox induced apoptosis in FTC-133 cells by trigging JNK pathway. This process was accompanied by a decrease of thrombospondin-1 (TSP-1) expression. Moreover, exogenous TSP-1 or its C-terminal-derived peptide interact with receptor CD47 and are able to protect FTC-133 cells against Dox-induced apoptosis. Here, we investigated the involvement of TSP-1/CD47 interaction in a context of acquired multidrug resistance in FTC-133 cells. To that end, we established a Dox-resistant cell line (FTC-133R cells) which developed a resistance against Dox-induced apoptosis. Cell viability was evaluated by Uptiblue assay, nuclear Dox was measured by microspectrofluorimetry, caspase activity was measured by fluorescence of cleaved caspase-3 substrate, gene expression was evaluated by RT-PCR and protein expression was examined by western-blot. Our results showed that FTC-133R overexpressed the P-gp and were 15-fold resistant to Dox. JNK phosphorylation and Dox-induced apoptosis were reduced in FTC-133R cells. Expression of CD47 was increased in FTC-133R cells but TSP-1 expression presented similar levels in two cell lines. VPL restored Dox nuclear uptake and FTC-133R cell sensitivity to apoptosis and induced a decrease in CD47 mRNA expression. Moreover, knockdown of CD47 in FTC-133R cells induced an increase in JNK activation and sensitized FTC-133R cells to Dox. Our data suggest that CD47 is able to contribute to the protection of FTC-133R cells against Dox-induced apoptosis and/or to potentiate the acquired Dox resistance.https://www.frontiersin.org/articles/10.3389/fonc.2020.551228/fullchemo-resistancedoxorubicinP-glycoproteinTSP-1CD47thyroid carcinoma cells
collection DOAJ
language English
format Article
sources DOAJ
author Marie-Pierre Courageot
Laurent Duca
Laurent Martiny
Emmanuelle Devarenne-Charpentier
Hamid Morjani
Hassan El Btaouri
spellingShingle Marie-Pierre Courageot
Laurent Duca
Laurent Martiny
Emmanuelle Devarenne-Charpentier
Hamid Morjani
Hassan El Btaouri
Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
Frontiers in Oncology
chemo-resistance
doxorubicin
P-glycoprotein
TSP-1
CD47
thyroid carcinoma cells
author_facet Marie-Pierre Courageot
Laurent Duca
Laurent Martiny
Emmanuelle Devarenne-Charpentier
Hamid Morjani
Hassan El Btaouri
author_sort Marie-Pierre Courageot
title Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
title_short Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
title_full Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
title_fullStr Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
title_full_unstemmed Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
title_sort thrombospondin-1 receptor cd47 overexpression contributes to p-glycoprotein-mediated multidrug resistance against doxorubicin in thyroid carcinoma ftc-133 cells
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2020-12-01
description It is now admitted that in addition to acquired resistance, the tumor microenvironment contributes to the development of chemo-resistance and malignant progression. In a previous study, we showed that Dox induced apoptosis in FTC-133 cells by trigging JNK pathway. This process was accompanied by a decrease of thrombospondin-1 (TSP-1) expression. Moreover, exogenous TSP-1 or its C-terminal-derived peptide interact with receptor CD47 and are able to protect FTC-133 cells against Dox-induced apoptosis. Here, we investigated the involvement of TSP-1/CD47 interaction in a context of acquired multidrug resistance in FTC-133 cells. To that end, we established a Dox-resistant cell line (FTC-133R cells) which developed a resistance against Dox-induced apoptosis. Cell viability was evaluated by Uptiblue assay, nuclear Dox was measured by microspectrofluorimetry, caspase activity was measured by fluorescence of cleaved caspase-3 substrate, gene expression was evaluated by RT-PCR and protein expression was examined by western-blot. Our results showed that FTC-133R overexpressed the P-gp and were 15-fold resistant to Dox. JNK phosphorylation and Dox-induced apoptosis were reduced in FTC-133R cells. Expression of CD47 was increased in FTC-133R cells but TSP-1 expression presented similar levels in two cell lines. VPL restored Dox nuclear uptake and FTC-133R cell sensitivity to apoptosis and induced a decrease in CD47 mRNA expression. Moreover, knockdown of CD47 in FTC-133R cells induced an increase in JNK activation and sensitized FTC-133R cells to Dox. Our data suggest that CD47 is able to contribute to the protection of FTC-133R cells against Dox-induced apoptosis and/or to potentiate the acquired Dox resistance.
topic chemo-resistance
doxorubicin
P-glycoprotein
TSP-1
CD47
thyroid carcinoma cells
url https://www.frontiersin.org/articles/10.3389/fonc.2020.551228/full
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