8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      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

          Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

          Related collections

          Most cited references109

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

          Oncogenic kinase signalling.

          Protein-tyrosine kinases (PTKs) are important regulators of intracellular signal-transduction pathways mediating development and multicellular communication in metazoans. Their activity is normally tightly controlled and regulated. Perturbation of PTK signalling by mutations and other genetic alterations results in deregulated kinase activity and malignant transformation. The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its downstream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70S6K), are crucial effectors in oncogenic PTK signalling. This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity and provides an update on our knowledge about the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Macrophages regulate the angiogenic switch in a mouse model of breast cancer.

            The development of a tumor vasculature or access to the host vasculature is a crucial step for the survival and metastasis of malignant tumors. Although therapeutic strategies attempting to inhibit this step during tumor development are being developed, the biological regulation of this process is still largely unknown. Using a transgenic mouse susceptible to mammary cancer, PyMT mice, we have characterized the development of the vasculature in mammary tumors during their progression to malignancy. We show that the onset of the angiogenic switch, identified as the formation of a high-density vessel network, is closely associated with the transition to malignancy. More importantly, both the angiogenic switch and the progression to malignancy are regulated by infiltrated macrophages in the primary mammary tumors. Inhibition of the macrophage infiltration into the tumor delayed the angiogenic switch and malignant transition whereas genetic restoration of the macrophage population specifically in these tumors rescued the vessel phenotype. Furthermore, premature induction of macrophage infiltration into premalignant lesions promoted an early onset of the angiogenic switch independent of tumor progression. Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inflammation: gearing the journey to cancer.

              Chronic inflammation plays a multifaceted role in carcinogenesis. Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. The possible mechanisms by which inflammation can contribute to carcinogenesis include induction of genomic instability, alterations in epigenetic events and subsequent inappropriate gene expression, enhanced proliferation of initiated cells, resistance to apoptosis, aggressive tumor neovascularization, invasion through tumor-associated basement membrane and metastasis, etc. Inflammation-induced reactive oxygen and nitrogen species cause damage to important cellular components (e.g., DNA, proteins and lipids), which can directly or indirectly contribute to malignant cell transformation. Overexpression, elevated secretion, or abnormal activation of proinflammatory mediators, such as cytokines, chemokines, cyclooxygenase-2, prostaglandins, inducible nitric oxide synthase, and nitric oxide, and a distinct network of intracellular signaling molecules including upstream kinases and transcription factors facilitate tumor promotion and progression. While inflammation promotes development of cancer, components of the tumor microenvironment, such as tumor cells, stromal cells in surrounding tissue and infiltrated inflammatory/immune cells generate an intratumoral inflammatory state by aberrant expression or activation of some proinflammatory molecules. Many of proinflammatory mediators, especially cytokines, chemokines and prostaglandins, turn on the angiogenic switches mainly controlled by vascular endothelial growth factor, thereby inducing inflammatory angiogenesis and tumor cell-stroma communication. This will end up with tumor angiogenesis, metastasis and invasion. Moreover, cellular microRNAs are emerging as a potential link between inflammation and cancer. The present article highlights the role of various proinflammatory mediators in carcinogenesis and their promise as potential targets for chemoprevention of inflammation-associated carcinogenesis.
                Bookmark

                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2016
                8 December 2016
                : 2016
                : 4917387
                Affiliations
                1CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal
                2Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal
                3Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
                4The Interuniversity Messerli Research Institute, The University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria
                5Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria
                6Center for the Study of Animal Sciences, CECA-ICETA, University of Porto, 4051-401 Porto, Portugal
                7Center for Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal
                Author notes
                *Felisbina L. Queiroga: fqueirog@ 123456utad.pt

                Academic Editor: Stephen H. Safe

                Author information
                http://orcid.org/0000-0002-8755-7826
                http://orcid.org/0000-0002-3902-5374
                http://orcid.org/0000-0001-6130-8381
                Article
                10.1155/2016/4917387
                5178344
                28053982
                7cd9e271-cbcb-4ba9-9c79-229545a95b54
                Copyright © 2016 Maria Isabel Carvalho et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 July 2016
                : 24 October 2016
                : 3 November 2016
                Funding
                Funded by: Fundação para a Ciência e a Tecnologia
                Award ID: OE/AGR/UI0772/2011
                Award ID: UID/AGR/04033/2013
                Award ID: SFRH/BD/78771/2011
                Funded by: Austrian Science Fund
                Award ID: SFB F4606-B28
                Categories
                Review Article

                Comments

                Comment on this article