bims-stacyt Biomed News
on Paracrine crosstalk between cancer and the organism
Issue of 2019‒09‒01
three papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. Semin Cancer Biol. 2019 Aug 21. pii: S1044-579X(19)30180-4. [Epub ahead of print]
    El Hassouni B, Granchi C, Vallés-Martí A, Supadmanaba IGP, Bononi G, Tuccinardi T, Funel N, Jimenez CR, Peters GJ, Giovannetti E, Minutolo F.
      Cancer metastasis to distant organs is initiated by tumor cells that disseminate from primary heterogeneous tumors. The subsequent growth and survival of tumor metastases depend on different metabolic changes, which constitute one of the enigmatic properties of tumor cells. Aerobic glycolysis, 'the Warburg effect', contributes to tumor energy supply, by oxidizing glucose in a faster manner compared to oxidative phosphorylation, leading to an increased lactate production by lactate dehydrogenase A (LDH-A), which in turn affects the immune response. Surrounding stromal cells contribute to feedback mechanisms further prompting the acquisition of pro-invasive metabolic features. Hence, therapeutic strategies targeting the glycolytic pathway are intensively investigated, with a special interest on their anti-metastatic properties. Various small molecules, such as LDH-A inhibitors, have shown pre-clinical activity against different cancer types, and blocking LDH-A could also help in designing future complimentary therapies. Modulation of specific targets in cells with an altered glycolytic metabolism should indeed result in a milder and distinct toxicity profile, compared to conventional cytotoxic therapy, while a combination treatment with vitamin C leading to increasing reactive oxygen species levels, should further inhibit cancer cell survival and invasion. In this review we describe the impact of metabolic reprogramming in cancer metastasis, the contribution of lactate in this aberrant process and its effect on oncogenic processes. Furthermore, we discuss experimental compounds that target glycolytic metabolism, such as LDH-A inhibitors, and their potential to improve current and experimental therapeutics against metastatic tumors.
    Keywords:  LDH; glycolysis; metastasis; tumor microenvironment; vitamin C
    DOI:  https://doi.org/10.1016/j.semcancer.2019.08.025
  2. Immunity. 2019 Aug 20. pii: S1074-7613(19)30327-9. [Epub ahead of print]
    Zhang D, Jin W, Wu R, Li J, Park SA, Tu E, Zanvit P, Xu J, Liu O, Cain A, Chen W.
      Diet has been suggested to be a potential environmental risk factor for the increasing incidence of autoimmune diseases, yet the underlying mechanisms remain elusive. Here, we show that high glucose intake exacerbated autoimmunity in mouse models of colitis and experimental autoimmune encephalomyelitis (EAE). We elucidated that high amounts of glucose specifically promoted T helper-17 (Th17) cell differentiation by activating transforming growth factor-β (TGF-β) from its latent form through upregulation of reactive oxygen species (ROS) in T cells. We further determined that mitochondrial ROS (mtROS) are key for high glucose-induced TGF-β activation and Th17 cell generation. We have thus revealed a previously unrecognized mechanism underlying the adverse effects of high glucose intake in the pathogenesis of autoimmunity and inflammation.
    Keywords:  CD4 T cells; EAE; IL-17; RORγt; ROS; T helper-17 cells; Th17; autoimmune diseases; colitis; high glucose; mitochondria; transforming growth factor-β
    DOI:  https://doi.org/10.1016/j.immuni.2019.08.001
  3. Adv Exp Med Biol. 2019 ;1155 857-867
    Lee H, Lee DS, Chang KJ, Kim SH, Cheong SH.
      We want to find the anti-neuroinflammatory action of the taurine derivative Glucose-Taurine Reduced (G-T-R). The anti-neuroinflammatory action by G-T-R were investigated in lipopolysaccharide (LPS)-induced BV2 microglia. G-T-R inhibited the production of nitric oxide and prostaglandin E2, and down-regulated the protein expression of inducible NO synthase and cyclooxygenase-2. In addition, G-T-R reduced the cytokines secretion such as tumor necrosis factor (TNF-α), interleukin (IL) -1β and IL-6, in BV2 microglia treated with LPS. In addition, G-T-R dose-dependently decreased the activation of nuclear factor-kappa B. These findings confirmed the anti-neuroinflammatory activity of G-T-R, which may exert protective effects against neuroinflammatory-related diseases.
    Keywords:  Anti-neuroinflammatory effects; BV2 microglia; Glucose-taurine reduced (G-T-R)
    DOI:  https://doi.org/10.1007/978-981-13-8023-5_72