WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner
by
Antonietta Notaro 1,†, Sonia Emanuele 1,†, Fabiana Geraci 2
, Antonella D’Anneo 2, Marianna Lauricella 1, Giuseppe Calvaruso 2 and Michela Giuliano 2,*
Antonietta Notaro 1,†, Sonia Emanuele 1,†, Fabiana Geraci 2, Antonella D’Anneo 2, Marianna Lauricella 1, Giuseppe Calvaruso 2 and Michela Giuliano 2,*
1
Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy
2
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 5235; https://doi.org/10.3390/ijms20205235
Received: 4 September 2019 / Revised: 9 October 2019 / Accepted: 18 October 2019 / Published: 22 October 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties. The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved. Using wound healing assay and zymography, we showed that WIN affects cell migration and reduces the activity of the metalloproteases MMP2 and MMP9. This effect seemed to be independent of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein involved in tissue remodeling and extracellular matrix deposition. SPARC release was indeed prevented by WIN, and SPARC silencing by RNA interference did not influence the effect of the cannabinoid on cell migration. WIN also increased the release of extracellular vesicles and dramatically upregulated miR-29b1, a key miRNA that modulates cell proliferation and migration. Interestingly, reduced cell migration was observed in stably miR-29b1-transfected cells, similarly to WIN-treated cells. Finally, we show the absence of SPARC in the extracellular vesicles released by osteosarcoma cells and no changes in SPARC level in miR-29b1 overexpressing cells. Overall, these findings suggest that WIN markedly affects cell migration, dependently on miR-29b1 and independently of SPARC, and can thus be considered as a potential innovative therapeutic agent in the treatment of osteosarcoma.
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Keywords:
osteosarcoma; cannabinoids; cell migration; miR-29b1; SPARC
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Notaro, A.; Emanuele, S.; Geraci, F.; D’Anneo, A.; Lauricella, M.; Calvaruso, G.; Giuliano, M. WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner. Int. J. Mol. Sci. 2019, 20, 5235.
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