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  • Oxidative damage to hyaluronan-CD44 interactions as an underlying mechanism of action of oxidative stress-inducing cancer therapy.

Oxidative damage to hyaluronan-CD44 interactions as an underlying mechanism of action of oxidative stress-inducing cancer therapy.

Redox biology (2021-04-26)
Maksudbek Yusupov, Angela Privat-Maldonado, Rodrigo M Cordeiro, Hanne Verswyvel, Priyanka Shaw, Jamoliddin Razzokov, Evelien Smits, Annemie Bogaerts
ABSTRACT

Multiple cancer therapies nowadays rely on oxidative stress to damage cancer cells. Here we investigated the biological and molecular effect of oxidative stress on the interaction between CD44 and hyaluronan (HA), as interrupting their binding can hinder cancer progression. Our experiments demonstrated that the oxidation of HA decreased its recognition by CD44, which was further enhanced when both CD44 and HA were oxidized. The reduction of CD44-HA binding negatively affected the proliferative state of cancer cells. Our multi-level atomistic simulations revealed that the binding free energy of HA to CD44 decreased upon oxidation. The effect of HA and CD44 oxidation on CD44-HA binding was similar, but when both HA and CD44 were oxidized, the effect was much larger, in agreement with our experiments. Hence, our experiments and computations support our hypothesis on the role of oxidation in the disturbance of CD44-HA interaction, which can lead to the inhibition of proliferative signaling pathways inside the tumor cell to induce cell death.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-CD44-PE antibody produced in mouse, clone MEM-85, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Hyaluronic acid sodium salt from rooster comb, avian glycosaminoglycan polysaccharide