The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression

Hyaluronan (HA) is a component of the extracellular matrix (ECM) it is the main non-sulfated glycosaminoglycan able to modulate cell behavior in the healthy and tumor context. Sulfated hyaluronan (sHA) is a biomaterial derived from chemical modifications of HA, since this molecule is not naturall...

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Autores principales: Spinelli, Fiorella Mercedes, Rosales, Paolo, Pluda, Stefano, Vitale, Daiana Luján, Icardi, Antonella, Guarise, Cristian, Reszegi, Andrea, Kovalszky, Ilona, García, Mariana, Sevic, Ina, Galesso, Devis, Alaniz, Laura
Otros Autores: 0000-0001-5593-9101
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2023
Materias:
Angiogenesis
Monocytes/macrophages
Sulfated hyaluronan
Tumor microenvironment
Acceso en línea:http://repositorio.unnoba.edu.ar/xmlui/handle/23601/635
Aporte de:
Re DI Repositorio Digital UNNOBA de Universidad Nacional del Noroeste de la Provincia de Buenos Aires
id I103-R405-23601-635
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 Angiogenesis
Monocytes/macrophages
Sulfated hyaluronan
Tumor microenvironment
spellingShingle Angiogenesis
Monocytes/macrophages
Sulfated hyaluronan
Tumor microenvironment
Spinelli, Fiorella Mercedes
Rosales, Paolo
Pluda, Stefano
Vitale, Daiana Luján
Icardi, Antonella
Guarise, Cristian
Reszegi, Andrea
Kovalszky, Ilona
García, Mariana
Sevic, Ina
Galesso, Devis
Alaniz, Laura
The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
topic_facet Angiogenesis
Monocytes/macrophages
Sulfated hyaluronan
Tumor microenvironment
description Hyaluronan (HA) is a component of the extracellular matrix (ECM) it is the main non-sulfated glycosaminoglycan able to modulate cell behavior in the healthy and tumor context. Sulfated hyaluronan (sHA) is a biomaterial derived from chemical modifications of HA, since this molecule is not naturally sulfated. The HA sulfation modifies several properties of the native molecule, acquiring antitumor properties in different cancers. In this study, we evaluated the action of sHA of 30–60 kDa with different degrees of sulfation (0.7 sHA1 and 2.5 sHA3) on tumor cells of a breast, lung, and colorectal cancer model and its action on other cells of the tumor microenvironment, such as endothelial and monocytes/macrophage cells. Our data showed that in breast and lung tumor cells, sHA3 is able to modulate cell viability, cytotoxicity, and proliferation, but no effects were observed on colorectal cancer cells. In 3D cultures of breast and lung cancer cells, sHA3 diminished the size of the tumorsphere and modulated total HA levels. In these tumor models, treatment of monocytes/ macrophages with sHA3 showed a downregulation of the expression of angiogenic factors. We also observed a decrease in endothelial cell migration and modulation of the hyaluronan-binding protein TSG-6. In the breast in vivo xenograft model, monocytes/macrophages preincubated with sHA1 or sHA3 decreased tumor vasculature, TSG-6 and HA levels. Besides, in silico analysis showed an association of TSG-6, HAS2, and IL-8 with biological processes implicated in the progression of the tumor. Taken together, our data indicate that sHA in a breast and lung tumor context is able to induce an antiangiogenic action on tumor cells as well as in onocytes/macrophages (Mo/MØ) by modulation of endothelial migration, angiogenic factors, and vessel formation.
author2 0000-0001-5593-9101
author_facet 0000-0001-5593-9101
Spinelli, Fiorella Mercedes
Rosales, Paolo
Pluda, Stefano
Vitale, Daiana Luján
Icardi, Antonella
Guarise, Cristian
Reszegi, Andrea
Kovalszky, Ilona
García, Mariana
Sevic, Ina
Galesso, Devis
Alaniz, Laura
format Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
author Spinelli, Fiorella Mercedes
Rosales, Paolo
Pluda, Stefano
Vitale, Daiana Luján
Icardi, Antonella
Guarise, Cristian
Reszegi, Andrea
Kovalszky, Ilona
García, Mariana
Sevic, Ina
Galesso, Devis
Alaniz, Laura
author_sort Spinelli, Fiorella Mercedes
title The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
title_short The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
title_full The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
title_fullStr The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
title_full_unstemmed The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression
title_sort effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: its role in angiogenesis and tumor progression
publishDate 2023
url http://repositorio.unnoba.edu.ar/xmlui/handle/23601/635
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spelling I103-R405-23601-6352025-10-21T21:12:39Z The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression Spinelli, Fiorella Mercedes Rosales, Paolo Pluda, Stefano Vitale, Daiana Luján Icardi, Antonella Guarise, Cristian Reszegi, Andrea Kovalszky, Ilona García, Mariana Sevic, Ina Galesso, Devis Alaniz, Laura 0000-0001-5593-9101 0000-0002-6070-6078 Angiogenesis Monocytes/macrophages Sulfated hyaluronan Tumor microenvironment Hyaluronan (HA) is a component of the extracellular matrix (ECM) it is the main non-sulfated glycosaminoglycan able to modulate cell behavior in the healthy and tumor context. Sulfated hyaluronan (sHA) is a biomaterial derived from chemical modifications of HA, since this molecule is not naturally sulfated. The HA sulfation modifies several properties of the native molecule, acquiring antitumor properties in different cancers. In this study, we evaluated the action of sHA of 30–60 kDa with different degrees of sulfation (0.7 sHA1 and 2.5 sHA3) on tumor cells of a breast, lung, and colorectal cancer model and its action on other cells of the tumor microenvironment, such as endothelial and monocytes/macrophage cells. Our data showed that in breast and lung tumor cells, sHA3 is able to modulate cell viability, cytotoxicity, and proliferation, but no effects were observed on colorectal cancer cells. In 3D cultures of breast and lung cancer cells, sHA3 diminished the size of the tumorsphere and modulated total HA levels. In these tumor models, treatment of monocytes/ macrophages with sHA3 showed a downregulation of the expression of angiogenic factors. We also observed a decrease in endothelial cell migration and modulation of the hyaluronan-binding protein TSG-6. In the breast in vivo xenograft model, monocytes/macrophages preincubated with sHA1 or sHA3 decreased tumor vasculature, TSG-6 and HA levels. Besides, in silico analysis showed an association of TSG-6, HAS2, and IL-8 with biological processes implicated in the progression of the tumor. Taken together, our data indicate that sHA in a breast and lung tumor context is able to induce an antiangiogenic action on tumor cells as well as in onocytes/macrophages (Mo/MØ) by modulation of endothelial migration, angiogenic factors, and vessel formation. 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: Rosales, Paolo. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Rosales, Paolo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Pluda, Stefano. Fidia Farmaceutici S.p.A.; Italia. 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: 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: Guarise, Cristian. Fidia Farmaceutici S.p.A.; Italia. Fil: Reszegi, Andrea. Semmelweis University. Department of Pathology and Experimental Cancer Research; Hungría. Fil: Kovalszky, Ilona. Semmelweis University. Department of Pathology and Experimental Cancer Research; Hungría. Fil: García, Mariana. Universidad Austral. IIMT–CONICET. Laboratorio de Terapia Génica; Argentina. Fil: Sevic, Ina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Microambiente Tumoral; Argentina. Fil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina. Fil: Galesso, Devis. Fidia Farmaceutici S.p.A.; Italia. 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 2023-12-04T19:33:26Z 2023-12-04T19:33:26Z 2022-01-31 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 Spinelli F. M., Rosales P., Pluda S., Vitale D. L., Icardi A., Guarise C., Reszegi A., Kovalszky I., García M., Sevic I., Galesso D., Alaniz L. (2022). The effects of sulfated hyaluronan in breast, lung and colorectal carcinoma and monocytes/macrophages cells: Its role in angiogenesis and tumor progression. IUBMB Life, 74(10), 927-942. 1521-6551 http://repositorio.unnoba.edu.ar/xmlui/handle/23601/635 eng eu-repo/grantAgreement/European Comission/H2020 RISE-MSCA Project/645,756/GLYCANC eu-repo/grantAgreement/UNNOBA/SIB 2019/0561-2019 eu-repo/grantAgreement/Fundación Roemmers 2018 doi: 10.1002/iub.2604 info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf IUBMB Life

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