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

DAIANA VITALE; KUMAR SAMPATH; ALANIZ LAURA; BURKHARD GREVE

FEBS JOURNAL

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2019

1742-464X

In contrast to the bulk of the tumor, a subset of cancer cells called cancer stem cells (or tumorinitiating cells) is characterized by the property of self-renewal, unlimited proliferative potential, expression of multidrug-resistance proteins, active DNA repair capacity, apoptosis resistance, and an enormous developmental plasticity. Due to these properties, cancer stem cells display increased resistance to chemo- and radiotherapy. Recent findings indicate that aberrant function of proteoglycans and glycosaminoglycans makes an important contribution to mediating the cancer stem cell phenotype and therapeutic resistance. For example, the large transmembrane chondroitin sulfateproteoglycan NG2 / CSPG4 marks stem cell populations in brain tumors. Cell surface heparan sulfate proteoglycans of the syndecan and glypican families modulate the stemness-associated Wnt,hedgehog and notch signaling pathways, whereas the interplay of hyaluronan in the stem cell nichewith cancer stem cell CD44 determines maintenance of stemness and promotes therapeutic resistance.A better understanding of the molecular mechanisms by which proteoglycans andglycosaminoglycans regulate cancer stem cell function will aid the development of targeted therapeutic approaches which avoid relapse after an otherwise successful conventional therapy.Chimeric antigen receptor T cells, proteoglycan-primed dendritic cells, proteoglycan-targeted antibody-drug conjugates and inhibitory peptides and glycans have already shown highly promising results in preclinical models.