Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Frontiers in Oncology Année : 2020

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

Résumé

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.

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hal-03372837 , version 1 (11-10-2021)

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Marie-Pierre Courageot, Laurent Duca, Laurent Martiny, Emmanuelle Devarenne-Charpentier, Hamid Morjani, et al.. Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells. Frontiers in Oncology, 2020, 10, ⟨10.3389/fonc.2020.551228⟩. ⟨hal-03372837⟩
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