15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      M-CSF and IL-34 expression as indicators for growth in sporadic vestibular schwannoma

      research-article

      Read this article at

          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

          Macrophage colony stimulating factor and IL-34 are associated with clinical vestibular schwannoma progression. Investigating the biology behind vestibular schwannoma progression helps understanding tumor growth. Inflammation is important in the microenvironment of neoplasms. Macrophages are major players in the intratumoral infiltrate. These tumor-associated macrophages are known to stimulate angiogenesis and cell growth. M-CSF and IL-34 are cytokines that can regulate tumor-infiltrating macrophages. They are expressed by tumors and form potential targets for therapy. The goal of this study was to investigate these cytokines in vestibular schwannomas and to see if their expression is related to angiogenesis, macrophage numbers, cystic degeneration, and volumetric tumor progression. Immunohistochemical expression of M-CSF and IL-34 was analyzed in ten fast-growing vestibular schwannomas and in ten slow-growing vestibular schwannomas. Expression M-CSF and IL-34 were compared between fast- versus slow-growing and cystic versus non-cystic tumors. Data on macrophage numbers and microvessel density, known from earlier research, was also included. All tumors expressed M-CSF and its expression was higher in fast-growing tumors ( p = 0.003) and in cystic tumors ( p = 0.035). CD163 expression was higher in tumors with strong M-CSF expression ( p = 0.003). All tumors expressed IL-34 as well, but no significant differences were found in relation to clinicopathological characteristics. This study demonstrated the expression of M-CSF and IL-34 in vestibular schwannomas. The results suggest that M-CSF is related to macrophage activity and tumor progression, making it a potential target for therapy. If a similar assumption can be made for IL-34 remains unclear.

          Related collections

          Most cited references23

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

          Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.

          Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease predisposing carriers to develop nervous system tumours. To identify the genetic defect, the region between two flanking polymorphic markers on chromosome 22 was cloned and several genes identified. One is the site of germ-line mutations in NF2 patients and of somatic mutations in NF2-related tumours. Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans.
            • Record: found
            • Abstract: found
            • Article: not found

            Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10.

            During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (M), one of the major leukocyte populations at the fetal-maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual M with an in vitro M differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) M markers expressed on human decidual M (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual M polarization. M-CSF/IL-10-stimulated and decidual M also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ-stimulated M produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 M-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual M, confirming that M-CSF/IL-10-induced M are closely related to decidual M. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual M with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.
              • Record: found
              • Abstract: found
              • Article: not found

              Jekyll and Hyde: the role of the microenvironment on the progression of cancer.

              It is now recognized that the host microenvironment undergoes extensive change during the evolution and progression of cancer. This involves the generation of cancer-associated fibroblasts (CAFs), which, through release of growth factors and cytokines, lead to enhanced angiogenesis, increased tumour growth and invasion. It has also been demonstrated that CAFs may modulate the cancer stem cell (CSC) phenotype, which has therapeutic implications. The altered fibroblast phenotype also contributes to the development of an altered extracellular matrix (ECM), with synthesis of ECM isoforms rarely found in normal tissues, including tenascin-C isoforms and the fibronectin EDA isoform. There is also emerging evidence of how the tensile strength of the tumour-associated ECM may be modified and lead to altered signalling in tumour cells. The hypoxic environment of the tumour stimulates angiogenesis and also impacts on other aspects of cell signalling, including the c-met pathway and lysyl oxidase-mediated signalling, which can directly promote tumour cell invasion. The inflammatory infiltrate associated with many solid tumours also modulates tumour function, having both anti- and pro-tumour effects. All of these components of the microenvironment provide potential targets for therapeutic attack, with a number of molecules already in clinical trials. It is also becoming evident that characterizing the tumour microenvironment can provide important prognostic and predictive information about tumours, independent of the tumour cell phenotype. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

                Author and article information

                Contributors
                (+31) 71 526 2559 , p.c.w.hogendoorn@lumc.nl
                Journal
                Virchows Arch
                Virchows Arch
                Virchows Archiv
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0945-6317
                1432-2307
                22 December 2018
                22 December 2018
                2019
                : 474
                : 3
                : 375-381
                Affiliations
                [1 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Pathology, , Leiden University Medical Center, ; P.O. Box 9600, 2300 RC Leiden, The Netherlands
                [2 ]ISNI 0000000089452978, GRID grid.10419.3d, Department of Otolaryngology, , Leiden University Medical Center, ; P.O. Box 9600, 2300 RC Leiden, The Netherlands
                Article
                2503
                10.1007/s00428-018-2503-1
                6515692
                30580386
                4c9b0dab-2679-4cab-bdf8-75bac35a78af
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 13 August 2018
                : 7 November 2018
                : 3 December 2018
                Funding
                Funded by: Leiden University Medical Center (LUMC)
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Pathology
                il-34,macrophage colony stimulating factor,vestibular schwannoma
                Pathology
                il-34, macrophage colony stimulating factor, vestibular schwannoma

                Comments

                Comment on this article

                Related Documents Log