bims-stacyt 2020-09-06 papers

J Oral Sci. 2020 Aug 31.

Glucose transporter 4 mediates LPS-induced IL-6 production in osteoblasts under high glucose conditions.

Shunichiro Kato, Natsuko Tanabe, Mayu Nagao, Jumpei Sekino, Keiko Tomita, Mayu Sakai, Kimiko Abe, Naoto Suzuki, Koichiro Ueda.

PURPOSE: Diabetes causes hyperglycemic disorders due to insufficient activity of insulin, and it also increases blood glucose level. Recent studies have reported the relationship between diabetes and periodontal disease. Periodontitis is advanced by inflammatory cytokines stimulated with LPS. The purpose of this study was to investigate the effects of hyperglycemia on the expression of inflammatory cytokines induced by LPS in osteoblasts.METHODS: Cells were cultured for 7 and 14 days in the presence or absence of LPS and glucose. The expression mRNA level of IL-6, RANKL and OCN was determined using real-time PCR. The protein expression of IL-6 and RANKL was also measured using ELISA.
RESULTS: LPS and glucose increased the mRNA expression of IL-6, coupled with a decrease in the mRNA expression of OCN, which is associated with IL-6 and glucose. It also increased the protein expression of IL-6 compared to LPS. However, LPS+Glucose did not affect the mRNA and protein expression of RANKL. Furthermore, GLUT4 inhibitor, WZB117, blocked the stimulatory effect of glucose on LPS-induced IL-6 mRNA expression. WZB117 did not affect LPS-reduced OCN mRNA expression.
CONCLUSION: These results suggest that high glucose levels increase LPS-induced IL-6 expression mediated by GLUT4.

Keywords: GLUT4; LPS; glucose; proinflammatory cytokine

DOI: https://doi.org/10.2334/josnusd.20-0010

Curr Opin Clin Nutr Metab Care. 2020 Aug 29.

Current mechanisms in obesity and tumor progression.

Andin Fosam, Rachel J Perry.

PURPOSE OF REVIEW: Hyperadiposity, as present in obesity, is a substantial threat to cancer risk and prognosis. Studies that have investigated the link between obesity and tumor progression have proposed several mechanistic frameworks, yet, these mechanisms are not fully defined. Further, a comprehensive understanding of how these various mechanisms may interact to create a dynamic disease state is lacking in the current literature.RECENT FINDINGS: Recent work has begun to explore not only discrete mechanisms by which obesity may promote tumor growth (for instance, metabolic and growth factor functions of insulin; inflammatory cytokines; adipokines; and others), but also how these putative tumor-promoting factors may interact.
SUMMARY: This review will highlight the present understanding of obesity, as it relates to tumor development and progression. First, we will introduce the impact of obesity in cancer within the dynamic tumor microenvironment, which will serve as a theme to frame this review. The core of this review will discuss recently proposed mechanisms that implicate obesity in tumor progression, including chronic inflammation and the role of pro-inflammatory cytokines, adipokines, hormones, and genetic approaches. Furthermore, we intend to offer current insight in targeting adipose tissue during the development of cancer prevention and treatment strategies.

DOI: https://doi.org/10.1097/MCO.0000000000000690

Biomedicines. 2020 Aug 27. pii: E310. [Epub ahead of print]8(9):

Investigating Glioblastoma Response to Hypoxia.

Agathe L Chédeville, Anbarasu Lourdusamy, Ana Rita Monteiro, Richard Hill, Patricia A Madureira.

Glioblastoma (GB) is the most common and deadly type of primary malignant brain tumor with an average patient survival of only 15-17 months. GBs typically have hypoxic regions associated with aggressiveness and chemoresistance. Using patient derived GB cells, we characterized how GB responds to hypoxia. We noted a hypoxia-dependent glycolytic switch characterized by the up-regulation of HK2, PFKFB3, PFKFB4, LDHA, PDK1, SLC2A1/GLUT-1, CA9/CAIX, and SLC16A3/MCT-4. Moreover, many proangiogenic genes and proteins, including VEGFA, VEGFC, VEGFD, PGF/PlGF, ADM, ANGPTL4, and SERPINE1/PAI-1 were up-regulated during hypoxia. We detected the hypoxic induction of invasion proteins, including the plasminogen receptor, S100A10, and the urokinase plasminogen activator receptor, uPAR. Furthermore, we observed a hypoxia-dependent up-regulation of the autophagy genes, BNIP-3 and DDIT4 and of the multi-functional protein, NDRG1 associated with GB chemoresistance; and down-regulation of EGR1 and TFRC (Graphical abstract). Analysis of GB patient cohorts' revealed differential expression of these genes in patient samples (except SLC16A3) compared to non-neoplastic brain tissue. High expression of SLC2A1, LDHA, PDK1, PFKFB4, HK2, VEGFA, SERPINE1, TFRC, and ADM was associated with significantly lower overall survival. Together these data provide important information regarding GB response to hypoxia which could support the development of more effective treatments for GB patients.

Keywords: autophagy; glioblastoma; glycolysis; hypoxia; invasion; tumor angiogenesis

DOI: https://doi.org/10.3390/biomedicines8090310