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

Title
Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance
Authors
Vitale, DaianaKatakam, Sampath KumarGreve, BurkhardJang, BoheeOh, Eok-SooAlaniz, LauraGoette, Martin
Ewha Authors
오억수장보희
SCOPUS Author ID
오억수scopus
Issue Date
2019
Journal Title
FEBS JOURNAL
ISSN
1742-464XJCR Link

1742-4658JCR Link
Citation
FEBS JOURNAL vol. 286, no. 15, pp. 2870 - 2882
Keywords
cancer stem cellCD44chemotherapyCSPG4heparan sulfatehyaluronanproteoglycanradiationstem cell nichesyndecan
Publisher
WILEY
Indexed
SCI; SCIE; SCOPUS WOS
Document Type
Review
Abstract
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.
DOI
10.1111/febs.14967
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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