| Autor: |
Snigireva AV; Institute of Cell Biophysics, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Morenkov OS; Institute of Cell Biophysics, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Skarga YY; Institute of Cell Biophysics, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Lisov AV; Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Lisova ZA; Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Leontievsky AA; Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Zhmurina MA; Institute of Cell Biophysics, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Petrenko VS; Institute of Cell Biophysics, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia., Vrublevskaya VV; Institute of Cell Biophysics, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Moscow Region, Russia. |
| Abstrakt: |
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. |
