A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate Inhibits the Basal and Hsp90-Stimulated Migration and Invasion of Tumor Cells

Autor: Anastasiya V. Snigireva, Oleg S. Morenkov, Yuri Y. Skarga, Alexander V. Lisov, Zoya A. Lisova, Alexey A. Leontievsky, Mariya A. Zhmurina, Viktoria S. Petrenko, Veronika V. Vrublevskaya
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Functional Biomaterials, Vol 11, Iss 2, p 39 (2020)
Druh dokumentu: article
ISSN: 2079-4983
DOI: 10.3390/jfb11020039
Popis: The extracellular cell surface-associated and soluble heat shock protein 90 (Hsp90) is known to participate in the migration and invasion of tumor cells. Earlier, we demonstrated that plasma membrane-associated heparan sulfate proteoglycans (HSPGs) bind the extracellular Hsp90 and thereby promote the Hsp90-mediated motility of tumor cells. Here, we showed that a conjugate of 2,5-dihydroxybenzoic acid with gelatin (2,5-DHBA–gelatin), a synthetic polymer with heparin-like properties, suppressed the basal (unstimulated) migration and invasion of human glioblastoma A-172 and fibrosarcoma HT1080 cells, which was accompanied by the detachment of a fraction of Hsp90 from cell surface HSPGs. The polymeric conjugate also inhibited the migration/invasion of cells stimulated by exogenous soluble native Hsp90, which correlated with the inhibition of the attachment of soluble Hsp90 to cell surface HSPGs. The action of the 2,5-DHBA–gelatin conjugate on the motility of A-172 and HT1080 cells was similar to that of heparin. The results demonstrate a potential of the 2,5-DHBA–gelatin polymer for the development of antimetastatic drugs targeting cell motility and a possible role of extracellular Hsp90 in the suppression of the migration and invasion of tumor cells mediated by the 2,5-DHBA–gelatin conjugate and heparin.
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