Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma
Abstract: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear recept...
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| Formato: | Artículo |
| Lenguaje: | Español |
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American Association for Cancer Research
2022
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/15399 |
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I33-R139-123456789-15399 |
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I33-R139-123456789-153992023-11-23T17:37:21Z Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma Cayrol, María Florencia Revuelta, Maria V. Debernardi, Maria Mercedes Paulazo, Maria Alejandra Phillip, Jude M. Zamponi, Nahuel Sterle, Helena Andrea Díaz Flaqué, María Celeste Magro, Cynthia Marullo, Rossella Mulvey, Erin Ruan, Jia Cremaschi, Graciela A. Cerchietti, Leandro INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO Abstract: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate the aVb3 integrin that is overexpressed in CTCL, potentially interfering the antineoplastic effect of bexarotene. We thus investigated the biological effect of levothyroxine in relation to bexarotene treatment. Although in isolated CTCL cells levothyroxine decreased, in an aVb3-dependent manner, the antineoplastic effect of bexarotene, levothyroxine supplementation in preclinical models was necessary to avoid suppression of lymphoma immunity. Accordingly, selective genetic and pharmacologic inhibition of integrin aVb3 improved the antineoplastic effect of bexarotene plus levothyroxine replacement while maintaining lymphoma immunity. Our results provide a mechanistic rationale for clinical testing of integrin aVb3 inhibitors as part of CTCL regimens based on bexarotene administration. 2022-11-04T14:37:41Z 2022-11-04T14:37:41Z 2022 Artículo Cayrol, M. F. et al. Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma [en línea]. Molecular cancer therapeutics, 2022, 21 (9). doi: 10.1158/1535-7163.MCT-22-0093. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/15399 1538-8514 (online) 1535-7163 (impreso) https://repositorio.uca.edu.ar/handle/123456789/15399 10.1158/1535-7163.MCT-22-0093 35793463 spa Acceso restringido http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research Molecular cancer therapeutics, 2022, 21 (9) |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Español |
| topic |
INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO |
| spellingShingle |
INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO Cayrol, María Florencia Revuelta, Maria V. Debernardi, Maria Mercedes Paulazo, Maria Alejandra Phillip, Jude M. Zamponi, Nahuel Sterle, Helena Andrea Díaz Flaqué, María Celeste Magro, Cynthia Marullo, Rossella Mulvey, Erin Ruan, Jia Cremaschi, Graciela A. Cerchietti, Leandro Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| topic_facet |
INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO |
| description |
Abstract: Bexarotene is a specific retinoid X receptor agonist that has been
used for the treatment of cutaneous T-cell lymphoma (CTCL).
Because bexarotene causes hypothyroidism, it requires the
administration of levothyroxine. However, levothyroxine, in
addition to its ubiquitous nuclear receptors, can activate
the aVb3 integrin that is overexpressed in CTCL, potentially
interfering the antineoplastic effect of bexarotene. We thus
investigated the biological effect of levothyroxine in relation
to bexarotene treatment. Although in isolated CTCL cells levothyroxine
decreased, in an aVb3-dependent manner, the antineoplastic
effect of bexarotene, levothyroxine supplementation in preclinical
models was necessary to avoid suppression of lymphoma immunity.
Accordingly, selective genetic and pharmacologic inhibition of
integrin aVb3 improved the antineoplastic effect of bexarotene
plus levothyroxine replacement while maintaining lymphoma
immunity. Our results provide a mechanistic rationale for clinical
testing of integrin aVb3 inhibitors as part of CTCL regimens based
on bexarotene administration. |
| format |
Artículo |
| author |
Cayrol, María Florencia Revuelta, Maria V. Debernardi, Maria Mercedes Paulazo, Maria Alejandra Phillip, Jude M. Zamponi, Nahuel Sterle, Helena Andrea Díaz Flaqué, María Celeste Magro, Cynthia Marullo, Rossella Mulvey, Erin Ruan, Jia Cremaschi, Graciela A. Cerchietti, Leandro |
| author_facet |
Cayrol, María Florencia Revuelta, Maria V. Debernardi, Maria Mercedes Paulazo, Maria Alejandra Phillip, Jude M. Zamponi, Nahuel Sterle, Helena Andrea Díaz Flaqué, María Celeste Magro, Cynthia Marullo, Rossella Mulvey, Erin Ruan, Jia Cremaschi, Graciela A. Cerchietti, Leandro |
| author_sort |
Cayrol, María Florencia |
| title |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| title_short |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| title_full |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| title_fullStr |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| title_full_unstemmed |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| title_sort |
inhibition of integrin avb3 signaling improves the antineoplastic effect of bexarotene in cutaneous t-cell lymphoma |
| publisher |
American Association for Cancer Research |
| publishDate |
2022 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/15399 |
| work_keys_str_mv |
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| _version_ |
1807949153636974592 |