Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression

Hyaluronan, the main glycosaminoglycan of extracellular matrices, is concentrated in tissues with high cell proliferation and migration rates. In cancer, hyaluronan expression is altered and it becomes fragmented into low-molecular-weight forms, affecting mechanisms associated with cell prolifera...

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Autores principales: Vitale, Daiana Luján, Spinelli, Fiorella Mercedes, Del Dago, Daiana, Icardi, Antonella, Demarchi, Gianina, Caon, Ilaria, García, Mariana, Bolontrade, Marcela, Passi, Alberto, Cristina, Carolina, Alaniz, Laura
Otros Autores: 0000-0001-5593-9101
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2023
Materias:
Hyaluronan
Cancer
Doxorubicin
Tumor microenvironment
Angiogenesis
Acceso en línea:http://repositorio.unnoba.edu.ar/xmlui/handle/23601/636
Aporte de:
Re DI Repositorio Digital UNNOBA de Universidad Nacional del Noroeste de la Provincia de Buenos Aires
id I103-R405-23601-636
record_format dspace
institution Universidad Nacional del Noroeste de la Provincia de Buenos Aires
institution_str I-103
repository_str R-405
collection Re DI Repositorio Digital UNNOBA
language Inglés
topic Hyaluronan
Cancer
Doxorubicin
Tumor microenvironment
Angiogenesis
spellingShingle Hyaluronan
Cancer
Doxorubicin
Tumor microenvironment
Angiogenesis
Vitale, Daiana Luján
Spinelli, Fiorella Mercedes
Del Dago, Daiana
Icardi, Antonella
Demarchi, Gianina
Caon, Ilaria
García, Mariana
Bolontrade, Marcela
Passi, Alberto
Cristina, Carolina
Alaniz, Laura
Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
topic_facet Hyaluronan
Cancer
Doxorubicin
Tumor microenvironment
Angiogenesis
description Hyaluronan, the main glycosaminoglycan of extracellular matrices, is concentrated in tissues with high cell proliferation and migration rates. In cancer, hyaluronan expression is altered and it becomes fragmented into low-molecular-weight forms, affecting mechanisms associated with cell proliferation, invasion, angiogenesis and multidrug resistance. Here, we analyzed the effect of low-molecular-weight hyaluronan on the response of T lymphoma, osteosarcoma, and mammary adenocarcinoma cell lines to the antineoplastic drug doxorubicin, and whether co-treatment with hyaluronan and doxorubicin modified the behavior of endothelial cells. Our aim was to associate the hyaluronan-doxorubicin response with angiogenic alterations in these tumors. After hyaluronan and doxorubicin co-treatment, hyaluronan altered drug accumulation and modulated the expression of ATP-binding cassette transporters in T-cell lymphoma cells. In contrast, no changes in drug accumulation were observed in cells from solid tumors, indicating that hyaluronan might not affect drug efflux. However, when we evaluated the effect on angiogenic mechanisms, the supernatant from tumor cells treated with doxorubicin exhibited a pro-angiogenic effect on endothelial cells. Hyaluronan-doxorubicin co-treatment increased migration and vessel formation in endothelial cells. This effect was independent of vascular endothelial growth factor but related to fibroblast growth factor-2 expression. Besides, we observed a proangiogenic effect on endothelial cells during hyaluronan and doxorubicin co-treatment in the in vivo murine model of T-cell lymphoma. Our results demonstrate for the first time that hyaluronan is a potential modulator of doxorubicin response by mechanisms that involve not only drug efflux but also angiogenic processes, providing an adverse tumor stroma during chemotherapy.
author2 0000-0001-5593-9101
author_facet 0000-0001-5593-9101
Vitale, Daiana Luján
Spinelli, Fiorella Mercedes
Del Dago, Daiana
Icardi, Antonella
Demarchi, Gianina
Caon, Ilaria
García, Mariana
Bolontrade, Marcela
Passi, Alberto
Cristina, Carolina
Alaniz, Laura
format Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
author Vitale, Daiana Luján
Spinelli, Fiorella Mercedes
Del Dago, Daiana
Icardi, Antonella
Demarchi, Gianina
Caon, Ilaria
García, Mariana
Bolontrade, Marcela
Passi, Alberto
Cristina, Carolina
Alaniz, Laura
author_sort Vitale, Daiana Luján
title Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
title_short Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
title_full Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
title_fullStr Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
title_full_unstemmed Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression
title_sort co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of vegf expression
publishDate 2023
url http://repositorio.unnoba.edu.ar/xmlui/handle/23601/636
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spelling I103-R405-23601-6362025-10-21T21:13:52Z Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression Vitale, Daiana Luján Spinelli, Fiorella Mercedes Del Dago, Daiana Icardi, Antonella Demarchi, Gianina Caon, Ilaria García, Mariana Bolontrade, Marcela Passi, Alberto Cristina, Carolina Alaniz, Laura 0000-0001-5593-9101 0000-0003-3328-3089 0000-0002-6070-6078 Hyaluronan Cancer Doxorubicin Tumor microenvironment Angiogenesis Hyaluronan, the main glycosaminoglycan of extracellular matrices, is concentrated in tissues with high cell proliferation and migration rates. In cancer, hyaluronan expression is altered and it becomes fragmented into low-molecular-weight forms, affecting mechanisms associated with cell proliferation, invasion, angiogenesis and multidrug resistance. Here, we analyzed the effect of low-molecular-weight hyaluronan on the response of T lymphoma, osteosarcoma, and mammary adenocarcinoma cell lines to the antineoplastic drug doxorubicin, and whether co-treatment with hyaluronan and doxorubicin modified the behavior of endothelial cells. Our aim was to associate the hyaluronan-doxorubicin response with angiogenic alterations in these tumors. After hyaluronan and doxorubicin co-treatment, hyaluronan altered drug accumulation and modulated the expression of ATP-binding cassette transporters in T-cell lymphoma cells. In contrast, no changes in drug accumulation were observed in cells from solid tumors, indicating that hyaluronan might not affect drug efflux. However, when we evaluated the effect on angiogenic mechanisms, the supernatant from tumor cells treated with doxorubicin exhibited a pro-angiogenic effect on endothelial cells. Hyaluronan-doxorubicin co-treatment increased migration and vessel formation in endothelial cells. This effect was independent of vascular endothelial growth factor but related to fibroblast growth factor-2 expression. Besides, we observed a proangiogenic effect on endothelial cells during hyaluronan and doxorubicin co-treatment in the in vivo murine model of T-cell lymphoma. Our results demonstrate for the first time that hyaluronan is a potential modulator of doxorubicin response by mechanisms that involve not only drug efflux but also angiogenic processes, providing an adverse tumor stroma during chemotherapy. Fil: Vitale, Daiana Luján. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Spinelli, Fiorella Mercedes. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Del Dago, Daiana. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Del Dago, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Icardi, Antonella. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Icardi, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Demarchi, Gianina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Fisiopatología de la Hipófisis; Argentina. Fil: Demarchi, Gianina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Caon, Ilaria. Università degli Studio dell’Insubria. Dipartimento di Medicina e Chirurgia; Italia. Fil: García, Mariana. Universidad Austral. IIMT–CONICET. Laboratorio de Terapia Génica; Argentina. Fil: Bolontrade, Marcela. Instituto de Biología y Medicina Experimental (IBYME-CONICET). Laboratorio de Células Madre; Argentina. Fil: Passi, Alberto. Università degli Studio dell’Insubria. Dipartimento di Medicina e Chirurgia; Italia. Fil: Cristina, Carolina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Fisiopatología de la Hipófisis; Argentina. Fil: Cristina, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Alaniz, Laura. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Alaniz, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Con referato 2023-12-04T19:49:47Z 2023-12-04T19:49:47Z 2018-11-27 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion Vitale D. L., Spinelli F. M, Del Dago D., Icardi A., Demarchi G., Caon I., García M., Bolontrade M. F., Passi A., Cristina C., Alaniz L. (2018). Co-treatment of tumor cells with hyaluronan plus doxorubicin affects endothelial cell behavior independently of VEGF expression. Oncotarget, 9(93), 36585-36602. 1949-2553 http://repositorio.unnoba.edu.ar/xmlui/handle/23601/636 eng eu-repo/grantAgreement/European Comission/H2020 RISE-MSCA Project/645,756/GLYCANC eu-repo/grantAgreement/Ministerio de Salud/Instituto Nacional del Cáncer/PIO 2015/ID31-2015 doi:10.18632/oncotarget.26379. info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf Oncotarget

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