bims-stacyt Biomed news
on Paracrine crosstalk between cancer and the organism
Issue of 2018‒07‒01
three papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. Biochem Biophys Res Commun. 2018 Jun 23. pii: S0006-291X(18)31427-X. [Epub ahead of print]
    Zhu J, Bing C, Wilding JPH.
      Metaflammation in adipose tissue, which is characterized by increased local gene expression and secretion of pro-inflammatory factors, may contribute to the increased risk of metabolic complications in obesity. It has been suggested that IL-1β might induce metaflammation in adipose tissue via modulating the NF-κB signaling pathway. In our study, the mRNA and secretion levels of major pro-inflammatory factors including IL (interleukin)-1β, IL-6, IL-8, MCP (monocyte chemoattractant protein)-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were measured as indicators of the inflammatory profile. We herein showed that IL-1β could induce adipose tissue metaflammation by enhancing the inflammatory profile of preadipocytes. Moreover, IL-1β could enhance pro-inflammatory gene expression by increasing the phosphorylation or decreasing the methylation of relA (NF-κB p65) of the NF-κB signaling pathway. VDR (vitamin D receptor) ligands have been shown to have anti-inflammatory properties in adipocytes. Likewise, our study demonstrated that the inflammatory profile of IL-1β-stimulated preadipocytes is significantly attenuated by VDR ligands 1α,25(OH)2D3, ZK159222 and ZK191785. Importantly, we showed that ZK159222 and ZK191785 could inhibit pro-inflammatory gene expression by decreasing the phosphorylation or increasing the methylation of relA. Furthermore, pro-inflammatory secretion could be reduced by 1α,25(OH)2D3, ZK159222 and ZK191785 via increasing the phosphorylation of eIF (eukaryotic translation initiation factor)-2α of the UPR (unfolded protein response) pathway. These observations suggest that the VDR ligands may be considered potential anti-inflammatory treatments for obesity associated metabolic complications.
    Keywords:  IL-1β; Inflammatory profile; Preadipocyte; VDR ligands; eIF-2α; relA
    DOI:  https://doi.org/10.1016/j.bbrc.2018.06.115
  2. Am J Pathol. 2018 Jun 20. pii: S0002-9440(18)30048-8. [Epub ahead of print]
    Tawiah A, Moreau F, Kumar M, Tiwari S, Falguera J, Chadee K.
      Intestinal epithelial cell wound healing involves cell migration, proliferation, and differentiation. Although numerous studies have analyzed the migration of absorptive epithelial cells during wound healing, it remains unclear how goblet cells restitute and how MUC2 mucin production affects this process. In this study, we examined the role of high MUC2 production in goblet cell migration during wound healing and demonstrated that during high MUC2 output, goblet cells migrated slower due to impaired production of wound healing factors and endoplasmic reticulum (ER) stress. Two goblet cell lines, HT29-H and HT29-L, that produced high and low MUC2 mucin, respectively, were used. HT29-L healed wounds faster than HT29-H cells by producing significantly higher amounts of FGF1, FGF2, VEGF-C, and MMP1. Predictably, treatment of HT29-H cells with recombinant FGF2 significantly enhanced migration and wound healing. High MUC2 biosynthesis in HT29-H cells induced ER stress and delayed migration that was abrogated by inhibiting ER stress with TUDCA and interleukin-22. FGF2 and interleukin-22-induced wound repair was dependent on STAT1 and STAT3 signaling. During wound healing after DSS-induced colitis, restitution of Math1M1GFP+ goblet cells occurred earlier in the proximal followed by the mid and then distal colon where ulceration was severe. We conclude that high MUC2 output during colitis impairs goblet cell migration and wound healing by reducing production of growth factors critical in wound repair.
    DOI:  https://doi.org/10.1016/j.ajpath.2018.05.013
  3. Semin Cancer Biol. 2018 Jun 20. pii: S1044-579X(18)30075-0. [Epub ahead of print]
    Missiaen R, Mazzone M, Bergers G.
      Tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and reciprocally regulated by paracrine signaling cues of cell constituents from both compartments. Formation and remodeling of new blood vessels in tumors is abnormal and facilitates immune evasion. In turn, immune cells in the tumor, specifically in context with an acidic and hypoxic environment, can promote neovascularization. Immunotherapy has emerged as a major therapeutic modality in cancer but is often hampered by the low influx of activated cytotoxic T-cells. On the other hand, anti-angiogenic therapy has been shown to transiently normalize the tumor vasculature and enhance infiltration of T lymphocytes, providing a rationale for a combination of these two therapeutic approaches to sustain and improve therapeutic efficacy in cancer. In this review, we discuss how the tumor vasculature facilitates an immunosuppressive phenotype and vice versa how innate and adaptive immune cells regulate angiogenesis during tumor progression. We further highlight recent results of antiangiogenic immunotherapies in experimental models and the clinic to evaluate the concept that targeting both the tumor vessels and immune cells increases the effectiveness in cancer patients.
    Keywords:  Angiogenesis; Immunosuppression; antiangiogenic therapy; immunotherapy immune checkpoint inhibitors; innate and adaptive immune cells; metabolism; tumor hypoxia and acidosis
    DOI:  https://doi.org/10.1016/j.semcancer.2018.06.002