Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance

In contrast to the bulk of the tumor, a subset of cancer cells called cancer stem cells (CSC; or tumor-initiating cells) is characterized by self-renewal, unlimited proliferative potential, expression of multidrug resistance proteins, active DNA repair capacity, apoptosis resistance, and a consid...

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Autores principales: Vitale, Daiana Luján, Katakam, Sampath Kumar, Greve, Burkhard, Jang, Bohee, Oh, Eok-Soo, Alaniz, Laura, Gotte, Martin
Otros Autores: 0000-0001-5593-9101
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2023
Materias:
Acceso en línea:http://repositorio.unnoba.edu.ar/xmlui/handle/23601/634
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id I103-R405-23601-634
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 Cancer stem cell
CD44
Chemotherapy
CSPG4
Heparan sulfate
Hyaluronan
Proteoglycan
Radiation
Stem cell niche
Syndecan
spellingShingle Cancer stem cell
CD44
Chemotherapy
CSPG4
Heparan sulfate
Hyaluronan
Proteoglycan
Radiation
Stem cell niche
Syndecan
Vitale, Daiana Luján
Katakam, Sampath Kumar
Greve, Burkhard
Jang, Bohee
Oh, Eok-Soo
Alaniz, Laura
Gotte, Martin
Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
topic_facet Cancer stem cell
CD44
Chemotherapy
CSPG4
Heparan sulfate
Hyaluronan
Proteoglycan
Radiation
Stem cell niche
Syndecan
description In contrast to the bulk of the tumor, a subset of cancer cells called cancer stem cells (CSC; or tumor-initiating cells) is characterized by self-renewal, unlimited proliferative potential, expression of multidrug resistance proteins, active DNA repair capacity, apoptosis resistance, and a considerable developmental plasticity. Due to these properties, CSCs display increased resistance to chemo- and radiotherapy. Recent findings indicate that aberrant functions of proteoglycans (PGs) and glycosaminoglycans (GAGs) contribute substantially to the CSC phenotype and therapeutic resistance. In this review, we summarize how the diverse functions of the glycoproteins and carbohydrates facilitate acquisition and maintenance of the CSC phenotype, and how this knowledge can be exploited to develop novel anticancer therapies. For example, the large transmembrane chondroitin sulfate PG NG2/ CSPG4 marks stem cell (SC) populations in brain tumors. Cell surface heparan sulfate PGs of the syndecan and glypican families modulate the stemness- associated Wnt, hedgehog, and notch signaling pathways, whereas the interplay of hyaluronan in the SC niche with CSC CD44 determines the maintenance of stemness and promotes therapeutic resistance. A better understanding of the molecular mechanisms by which PGs and GAGs regulate CSC function will aid the development of targeted therapeutic approaches which could avoid relapse after an otherwise successful conventional therapy. Chimeric antigen receptor T cells, PG-primed dendritic cells, PG-targeted antibody–drug conjugates, and inhibitory peptides and glycans have already shown highly promising results in preclinical models.
author2 0000-0001-5593-9101
author_facet 0000-0001-5593-9101
Vitale, Daiana Luján
Katakam, Sampath Kumar
Greve, Burkhard
Jang, Bohee
Oh, Eok-Soo
Alaniz, Laura
Gotte, Martin
format Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
author Vitale, Daiana Luján
Katakam, Sampath Kumar
Greve, Burkhard
Jang, Bohee
Oh, Eok-Soo
Alaniz, Laura
Gotte, Martin
author_sort Vitale, Daiana Luján
title Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
title_short Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
title_full Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
title_fullStr Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
title_full_unstemmed Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
title_sort proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
publishDate 2023
url http://repositorio.unnoba.edu.ar/xmlui/handle/23601/634
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AT katakamsampathkumar proteoglycansandglycosaminoglycansasregulatorsofcancerstemcellfunctionandtherapeuticresistance
AT greveburkhard proteoglycansandglycosaminoglycansasregulatorsofcancerstemcellfunctionandtherapeuticresistance
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spelling I103-R405-23601-6342025-10-21T21:11:39Z Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance Vitale, Daiana Luján Katakam, Sampath Kumar Greve, Burkhard Jang, Bohee Oh, Eok-Soo Alaniz, Laura Gotte, Martin 0000-0001-5593-9101 0000-0002-6070-6078 0000-0003-2360-2496 Cancer stem cell CD44 Chemotherapy CSPG4 Heparan sulfate Hyaluronan Proteoglycan Radiation Stem cell niche Syndecan In contrast to the bulk of the tumor, a subset of cancer cells called cancer stem cells (CSC; or tumor-initiating cells) is characterized by self-renewal, unlimited proliferative potential, expression of multidrug resistance proteins, active DNA repair capacity, apoptosis resistance, and a considerable developmental plasticity. Due to these properties, CSCs display increased resistance to chemo- and radiotherapy. Recent findings indicate that aberrant functions of proteoglycans (PGs) and glycosaminoglycans (GAGs) contribute substantially to the CSC phenotype and therapeutic resistance. In this review, we summarize how the diverse functions of the glycoproteins and carbohydrates facilitate acquisition and maintenance of the CSC phenotype, and how this knowledge can be exploited to develop novel anticancer therapies. For example, the large transmembrane chondroitin sulfate PG NG2/ CSPG4 marks stem cell (SC) populations in brain tumors. Cell surface heparan sulfate PGs of the syndecan and glypican families modulate the stemness- associated Wnt, hedgehog, and notch signaling pathways, whereas the interplay of hyaluronan in the SC niche with CSC CD44 determines the maintenance of stemness and promotes therapeutic resistance. A better understanding of the molecular mechanisms by which PGs and GAGs regulate CSC function will aid the development of targeted therapeutic approaches which could avoid relapse after an otherwise successful conventional therapy. Chimeric antigen receptor T cells, PG-primed dendritic cells, PG-targeted antibody–drug conjugates, and inhibitory peptides and glycans have already shown highly promising results in preclinical models. 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: Katakam, Sampath Kumar. Munster University. Munster University Hospital. Department of Gynecology and Obstetrics; Alemania. Fil: Greve, Burkhard. Munster University. Munster University Hospital. Department of Radiotherapy – Radiooncology; Alemania. Fil: Jang, Bohee. Ewha Womans University. Department of Life Sciences. The Research Center for Cellular Homeostasis; Corea. Fil: Oh, Eok-Soo. Ewha Womans University. Department of Life Sciences. The Research Center for Cellular Homeostasis; Corea. 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. Fil: Gotte, Martin. Munster University. Munster University Hospital. Department of Gynecology and Obstetrics; Alemania. Con referato 2023-12-04T19:18:39Z 2023-12-04T19:18:39Z 2019-06-19 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., Kumar Katakam S., Greve B., Jang B., Oh E. S.Alaniz L., Götte M. (2019). Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance. The FEBS Journal, 286(15), 2870-2882 1742-4658 http://repositorio.unnoba.edu.ar/xmlui/handle/23601/634 eng eu-repo/grantAgreement/European Comission/H2020 RISE-MSCA Project/645,756/GLYCANC doi:10.1111/febs.14967 info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf application/vnd.openxmlformats-officedocument.wordprocessingml.document The FEBS Journal