Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

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 Bobesity^ environment, that can be explored for the understanding of cancer cells biology, for the search of biomarkers, prognostic markers and therapeutic approaches.

NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas

“…At present, there very few reports on the mechanism of action of adipokines in gliomas . We report coexpression of NAMPT, GRN, RETN, IL6, SERPINE1, and CCL2 in LGG and GBM and it seems that they are coexpressed in gliomas playing significant roles in glioma establishment and progression .…”

“…At present, there very few reports on the mechanism of action of adipokines in gliomas. 36 We report coexpression of NAMPT, GRN, RETN, IL6, SERPINE1, and CCL2 in LGG and GBM and it seems that they are coexpressed in gliomas playing significant roles in glioma establishment and progression. 37 Mohammadi et al 37 reported synergistic effects of RETN and NAMPT on telomerase gene expression and acceleration of tumor growth in gastric cancer cells.…”

Putting Proteomics Into Immunotherapy for Glioblastoma

“…Some identified factors from adipocyte cells are found underexpressed, such as STI1, hnRNPs, and PGK1 in conditioned glioma cells, and some are found upregulated in contrast, such as RFC1, KIF5C, ANXA2, N-RAP, and RACK1 in GL261 cell. In addition, pro-inflammatory and angiogenic factors are also with different regulations (107). A proteomics research on mouse glial culture indicated that glial cells will activate the MAPK/ERK pathway and upregulate a variety of proteins participating in inflammation, cell adhesion, and extracellular structural organization after exposure to GBM cells (108).…”

Associations of General and Abdominal Obesity with the Risk of Glioma Development

“…While obesity is a well-known risk factor for developing various types of cancer [7,8], conflicting results have been reported concerning the relationship between obesity and the risk of glioma in prospective cohort studies, case-control studies, and meta-analyses [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, a recent biological study suggested that adipocyte-released factors can promote the growth and progression of glioma cells [24]. Recent clinical studies also supported potential associations between body composition and progression of tumors in patients with brain malignancies [25,26].…”