Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma
- Autores
- 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
- Año de publicación
- 2022
- Idioma
- español castellano
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Cayrol, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Revuelta, Maria V. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos
Fil: Debernardi, Maria Mercedes. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Debernardi, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Paulazo, Maria Alejandra. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Paulazo, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Phillip, Jude M. Johns Hopkins University. Institute for Nanobiotechnology. Chemical and Biomolecular Engineering, Oncology. Departments of Biomedical Engineering; Estados Unidos
Fil: Zamponi, Nahuel. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos
Fil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Sterle, Helena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Magro, Cynthia. Weill Cornell Medicine, Department of Pathology and Laboratory Medicine; Estados Unidos
Fil: Marullo, Rossella. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos
Fil: Mulvey, Erin. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos
Fil: Ruan, Jia. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos
Fil: Cremaschi, Graciela A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina
Fil: Cerchietti, Leandro. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos
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. - Fuente
- Molecular cancer therapeutics, 2022, 21 (9)
- Materia
-
INMUNOLOGIA
LINFOMA DE CÉLULAS T
BEXAROTENO - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
.jpg)
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/15399
Ver los metadatos del registro completo
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Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell LymphomaCayrol, María FlorenciaRevuelta, Maria V.Debernardi, Maria MercedesPaulazo, Maria AlejandraPhillip, Jude M.Zamponi, NahuelSterle, Helena AndreaDíaz Flaqué, María CelesteMagro, CynthiaMarullo, RossellaMulvey, ErinRuan, JiaCremaschi, Graciela A.Cerchietti, LeandroINMUNOLOGIALINFOMA DE CÉLULAS TBEXAROTENOFil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; ArgentinaFil: Cayrol, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Revuelta, Maria V. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados UnidosFil: Debernardi, Maria Mercedes. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; ArgentinaFil: Debernardi, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paulazo, Maria Alejandra. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; ArgentinaFil: Paulazo, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Phillip, Jude M. Johns Hopkins University. Institute for Nanobiotechnology. Chemical and Biomolecular Engineering, Oncology. Departments of Biomedical Engineering; Estados UnidosFil: Zamponi, Nahuel. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados UnidosFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; ArgentinaFil: Sterle, Helena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; ArgentinaFil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Magro, Cynthia. Weill Cornell Medicine, Department of Pathology and Laboratory Medicine; Estados UnidosFil: Marullo, Rossella. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados UnidosFil: Mulvey, Erin. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados UnidosFil: Ruan, Jia. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados UnidosFil: Cremaschi, Graciela A. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; ArgentinaFil: Cerchietti, Leandro. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados UnidosAbstract: 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.American Association for Cancer Research2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/153991538-8514 (online)1535-7163 (impreso)10.1158/1535-7163.MCT-22-009335793463Cayrol, 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/123456789/15399Molecular cancer therapeutics, 2022, 21 (9)reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaspainfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:58:57Zoai:ucacris:123456789/15399instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:58:57.86Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse |
| dc.title.none.fl_str_mv |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| title |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma |
| spellingShingle |
Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma Cayrol, María Florencia INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO |
| 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 |
| dc.creator.none.fl_str_mv |
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 |
Cayrol, María Florencia |
| 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_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO |
| topic |
INMUNOLOGIA LINFOMA DE CÉLULAS T BEXAROTENO |
| dc.description.none.fl_txt_mv |
Fil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Cayrol, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Revuelta, Maria V. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Debernardi, Maria Mercedes. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Debernardi, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Paulazo, Maria Alejandra. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Paulazo, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Phillip, Jude M. Johns Hopkins University. Institute for Nanobiotechnology. Chemical and Biomolecular Engineering, Oncology. Departments of Biomedical Engineering; Estados Unidos Fil: Zamponi, Nahuel. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Sterle, Helena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Magro, Cynthia. Weill Cornell Medicine, Department of Pathology and Laboratory Medicine; Estados Unidos Fil: Marullo, Rossella. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Mulvey, Erin. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Ruan, Jia. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Cremaschi, Graciela A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Cerchietti, Leandro. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos 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. |
| description |
Fil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina |
| publishDate |
2022 |
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2022 |
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article |
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publishedVersion |
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https://repositorio.uca.edu.ar/handle/123456789/15399 1538-8514 (online) 1535-7163 (impreso) 10.1158/1535-7163.MCT-22-0093 35793463 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 |
| url |
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1538-8514 (online) 1535-7163 (impreso) 10.1158/1535-7163.MCT-22-0093 35793463 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 |
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American Association for Cancer Research |
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