59
views
0
recommends
+1 Recommend
1 collections
    1
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

      , 1 , 2 , 3 , * , 1 , 2 , 4

      4open

      EDP Sciences

      Adenoma, Adhesion, Akt, ALOX, Apoptosis, Aquaporin, Autophagy, Bacterium, BIM, Blastoma, Cancer, Carcinoma, Carcinogenesis, CCC, Cdc42, Cdk2, Cholangiocellular carcinoma, Crohn's disease, Chronic inflammation, Colitis, Colorectal cancer, COX, Cyclin, Cyclooxygenase, CYP, Cytochrome P450, Cytokine, CXCR4, E2F4/5, E-cadherin, Eicosanoide, EBV, Epstein–Barr virus, ERK, ETE, Fibroblast, Fibrosis, Fluke, FOXO3a, Gastric cancer, Gastritis, Glycocalyx, HBV, HCV, Helicobacter pylori , Hepatitis B virus, Hepatitis C virus, HETE, Homeostasis, HCC, HIV, HPV, HSV, Human herpes virus, Human papilloma virus, IBD, ICAM, IDO, IL, IL-β1, Interleukin, Inflammation, Leukemia, Lipoxygenase, LTA4, LTB4, LTC4, LTD4, LTE4, Liver cancer, LOX, LOXL3, Lymphoma, Lysyl oxidase, MAPK, MDA, Metalloproteinase, MMP, Mutation, NF-κB, AP1, API2, PCN, PGD2, PGG2, PGH2, PGFF2a, Phagocytes, PI3K, Polyp, Precancerous niche, Prostate cancer, PUMA, Rac1, RNS, ROS, Sarcoma, SPhK, S1P, S1PR3, Simvastatin, SK2, SOX, Tissue, TGF, TNF, TOR, TXA2, VCAM, Virus, VZV

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.

          Related collections

          Most cited references 265

          • Record: found
          • Abstract: found
          • Article: not found

          APC mutations occur early during colorectal tumorigenesis.

          Human tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumour suppressor genes. But in no common adult cancer have the mutations that are critical in the early stages of the tumorigenic process been defined. We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from small benign tumours (adenomas) to larger malignant tumours (carcinomas) over the course of several decades. Here we report that sequence analysis of 41 colorectal tumours revealed that the majority of colorectal carcinomas (60%) and adenomas (63%) contained a mutated APC gene. Furthermore, the APC gene met two criteria of importance for tumour initiation. First, mutations of this gene were found in the earliest tumours that could be analysed, including adenomas as small as 0.5 cm in diameter. Second, the frequency of such mutations remained constant as tumours progressed from benign to malignant stages. These data provide strong evidence that mutations of the APC gene play a major role in the early development of colorectal neoplasms.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cytoplasmic chromatin triggers inflammation in senescence and cancer

            Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing 1–3 . However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence 4,5 , a form of terminal cell cycle arrest associated with pro-inflammatory responses 6 . The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA sensing cGAS-STING pathway, leading to both short-term inflammation to restrain activated oncogene and chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption.

              Aquaporin-1 (AQP1) is a water channel protein expressed widely in vascular endothelia, where it increases cell membrane water permeability. The role of AQP1 in endothelial cell function is unknown. Here we show remarkably impaired tumour growth in AQP1-null mice after subcutaneous or intracranial tumour cell implantation, with reduced tumour vascularity and extensive necrosis. A new mechanism for the impaired angiogenesis was established from cell culture studies. Although adhesion and proliferation were similar in primary cultures of aortic endothelia from wild-type and from AQP1-null mice, cell migration was greatly impaired in AQP1-deficient cells, with abnormal vessel formation in vitro. Stable transfection of non-endothelial cells with AQP1 or with a structurally different water-selective transporter (AQP4) accelerated cell migration and wound healing in vitro. Motile AQP1-expressing cells had prominent membrane ruffles at the leading edge with polarization of AQP1 protein to lamellipodia, where rapid water fluxes occur. Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration.
                Bookmark

                Author and article information

                Journal
                fopen
                https://www.4open-sciences.org
                4open
                4open
                EDP Sciences
                2557-0250
                25 April 2019
                25 April 2019
                2019
                : 2
                : ( publisher-idID: fopen/2019/01 )
                Affiliations
                [1 ] Theodor-Billroth-Academy®, , Germany, USA,
                [2 ] INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, , Germany, USA,
                [3 ] Department of Surgery, Carl-Thiem-Klinikum, , Cottbus, Germany,
                [4 ] Risk-Based Decisions Inc., , Sacramento, CA, USA,
                Author notes
                [* ]Corresponding author: b-bruecher@ 123456gmx.de
                Article
                fopen180014
                10.1051/fopen/2018006
                © B.L.D.M. Brücher and I.S. Jamall, Published by EDP Sciences 2019

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 305, Pages: 22
                Product
                Self URI (journal page): https://www.4open-sciences.org/
                Categories
                Life Sciences - Medicine
                Disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”
                Review Article
                Custom metadata
                4open 2019, 2, 8
                2019
                2019
                2019

                Comments

                Comment on this article