4.5 Article

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

Journal

METABOLIC BRAIN DISEASE
Volume 34, Issue 1, Pages 141-152

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-018-0327-y

Keywords

Adipo-proteomics; GL261; Glioma; Obesity

Funding

  1. ERASMUS grant
  2. Italian Government
  3. AIRC [10807]
  4. PNR-CNR Aging Program
  5. FCT [UID/BIM/04293/2013]
  6. Portuguese Government [FCT.SFRH/BD/80434/2011]
  7. [SAICT-POL/24325/2016]
  8. [SAICT-POL/24358/2016]
  9. Fundação para a Ciência e a Tecnologia [SAICT-POL/24325/2016, SAICT-POL/24358/2016] Funding Source: FCT

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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-, 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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