Abstract
Gliomas represent the most common primary malignant brain tumors in adults, with an extremely poor prognosis. Among several risk factors, lifestyle was also recently identified as a major risk factor for the development of primary glioma. In the present study, we explore the relationship between obesity and glioma in a cellular model. Thus, we have study the influence of adipocytes secretome on glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned medium (adipokines-enriched medium), we showed that adipocyte-released factors relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI-TOF-MS and proteomic array analysis. In a first view, STI1, hnRNPs and PGK1 are under expressed on CGl. Similarly, both carbonic anhydrase and aldose reductase are even suppressed in glioma cells that grown under adipokines-enriched environment. Contrariwise, RFC1, KIF5C, ANXA2, N-RAP and RACK1 are overexpressed in GL261 cell the in the presence of the adipokines-enriched medium. We further identified the factors that are released by adipocyte cells, and revealed that several pro-inflammatory and angiogenic factors, such as IL-6, IL-11, LIF, PAI-1, TNF-α, endocan, HGF, VEGF IGF-I, were secreted to the medium into a high extent, whereas TIMP-1 and SerpinE1 were under expressed on CGl. This study discloses an interesting in vitro model for the study of glioma biology under a “obesity” environment, that can be explored for the understanding of cancer cells biology, for the search of biomarkers, prognostic markers and therapeutic approaches.
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Acknowledgements
Fernandes R. on the behalf of the authors deeply acknowledge Prof. Pedroso Lima, CNC, Coimbra, Portugal by her kindness in providing the GL261 cells. Costa J. and Fernandes R. were supported with an ERASMUS grant. Portuguese Government supported Coelho P. with a PhD grant by FCT. SFRH/BD/80434/2011. Italian Government supported Sala C. with an AIRC grant n. 10807 and PNR-CNR Aging Program 2012-2014. The project was partially supported by FCT (Strategic Project Reference: UID/BIM/04293/2013). Fernandes R. is support by SAICT-POL/24325/2016 and SAICT-POL/24358/2016.
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Conception: Rúben Fernandes; Research design: Rúben Fernandes and Carlo Sala; Manuscript writing: Joana Almeida and Joana Costa which contributed equally and Pedro Coelho; Research and data analysis: Joana Almeida, Joana Costa, Pedro Coelho, Valentina Cea, Marco Galésio, João Paulo Noronha, Mário Diniz, Cristina Prudêncio, Raquel Soares, Carlo Sala and Rúben Fernandes. All authors have read and approved the final manuscript.
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No human participants, tissues or cells were used, other than commercially available cell lines, that require prior ethical approval to the corresponding ethic committees.
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Almeida, J., Costa, J., Coelho, P. et al. Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma. Metab Brain Dis 34, 141–152 (2019). https://doi.org/10.1007/s11011-018-0327-y
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DOI: https://doi.org/10.1007/s11011-018-0327-y