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Cancers 2019, 11(1), 88; https://doi.org/10.3390/cancers11010088

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

1
Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, 07122 Palma de Mallorca, Spain
2
Lipopharma Therapeutics, Isaac Newton, 07121 Palma de Mallorca, Spain
These authors contributed equally to this work
*
Author to whom correspondence should be addressed.
Received: 10 December 2018 / Revised: 31 December 2018 / Accepted: 8 January 2019 / Published: 14 January 2019
PDF [1287 KB, uploaded 14 January 2019]

Abstract

Background: 2-Hydroxyoleic acid (2OHOA) is particularly active against glioblastoma multiforme (GBM) and successfully finished a phase I/IIA trial in patients with glioma and other advanced solid tumors. However, its mechanism of action is not fully known. Methods: The relationship between SMS1 and SMS2 expressions (mRNA) and overall survival in 329 glioma patients was investigated, and so was the correlation between SMS expression and 2OHOA’s efficacy. The opposing role of SMS isoforms in 2OHOA’s mechanism of action and in GBM cell growth, differentiation and death, was studied overexpressing or silencing them in human GBM cells. Results: Patients with high-SMS1 plus low-SMS2 expression had a 5-year survival ~10-fold higher than patients with low-SMS1 plus high-SMS2 expression. SMS1 and SMS2 also had opposing effect on GBM cell survival and 2OHOA’s IC50 correlated with basal SMS1 levels and treatment induced changes in SMS1/SMS2 ratio. SMSs expression disparately affected 2OHOA’s cancer cell proliferation, differentiation, ER-stress and autophagy. Conclusions: SMS1 and SMS2 showed opposite associations with glioma patient survival, glioma cell growth and response to 2OHOA treatment. SMSs signature could constitute a valuable prognostic biomarker, with high SMS1 and low SMS2 being a better disease prognosis. Additionally, low basal SMS1 mRNA levels predict positive response to 2OHOA.
Keywords: SMS1; SMS2; glioma; biomarker; 2OHOA SMS1; SMS2; glioma; biomarker; 2OHOA
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 (CC BY 4.0).

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Fernández-García, P.; Rosselló, C.A.; Rodríguez-Lorca, R.; Beteta-Göbel, R.; Fernández-Díaz, J.; Lladó, V.; Busquets, X.; Escribá, P.V. The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA. Cancers 2019, 11, 88.

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