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      Drosophila as a model to study the role of blood cells in inflammation, innate immunity and cancer

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          Abstract

          Drosophila has a primitive yet effective blood system with three types of haemocytes which function throughout different developmental stages and environmental stimuli. Haemocytes play essential roles in tissue modeling during embryogenesis and morphogenesis, and also in innate immunity. The open circulatory system of Drosophila makes haemocytes ideal signal mediators to cells and tissues in response to events such as infection and wounding. The application of recently developed and sophisticated genetic tools to the relatively simple genome of Drosophila has made the fly a popular system for modeling human tumorigensis and metastasis. Drosophila is now used for screening and investigation of genes implicated in human leukemia and also in modeling development of solid tumors. This second line of research offers promising opportunities to determine the seemingly conflicting roles of blood cells in tumor progression and invasion. This review provides an overview of the signaling pathways conserved in Drosophila during haematopoiesis, haemostasis, innate immunity, wound healing and inflammation. We also review the most recent progress in the use of Drosophila as a cancer research model with an emphasis on the roles haemocytes can play in various cancer models and in the links between inflammation and cancer.

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          Most cited references160

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          Cutaneous wound healing.

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            Macrophage regulation of tumor responses to anticancer therapies.

            Tumor-associated macrophages (TAMs) promote key processes in tumor progression, like angiogenesis, immunosuppression, invasion, and metastasis. Increasing studies have also shown that TAMs can either enhance or antagonize the antitumor efficacy of cytotoxic chemotherapy, cancer-cell targeting antibodies, and immunotherapeutic agents--depending on the type of treatment and tumor model. TAMs also drive reparative mechanisms in tumors after radiotherapy or treatment with vascular-targeting agents. Here, we discuss the biological significance and clinical implications of these findings, with an emphasis on novel approaches that effectively target TAMs to increase the efficacy of such therapies. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut.

              Cells in intestinal epithelia turn over rapidly due to damage from digestion and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to replenish the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with epithelial cell loss. We show here that when enterocytes (ECs) in the Drosophila midgut are subjected to apoptosis, enteric infection, or JNK-mediated stress signaling, they produce cytokines (Upd, Upd2, and Upd3) that activate Jak/Stat signaling in ISCs, promoting their rapid division. Upd/Jak/Stat activity also promotes progenitor cell differentiation, in part by stimulating Delta/Notch signaling, and is required for differentiation in both normal and regenerating midguts. Hence, cytokine-mediated feedback enables stem cells to replace spent progeny as they are lost, thereby establishing gut homeostasis.
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                Author and article information

                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                09 January 2014
                2013
                : 3
                : 113
                Affiliations
                Laboratory of Genes and Development, Department of Biochemistry, University of Oxford Oxford, UK
                Author notes

                Edited by: Yiorgos Apidianakis, University of Cyprus, Cyprus

                Reviewed by: Sung O. Kim, University of Western Ontario, Canada; Valerio Iebba, ‘Sapienza’ University of Rome, Italy

                *Correspondence: Petros Ligoxygakis, Laboratory of Genes and Development, Department of Biochemistry, University of Oxford, New Biochemistry Building, South Parks Road, Oxford OX1 3QU, UK e-mail: petros.ligoxygakis@ 123456bioch.ox.ac.uk

                This article was submitted to the journal Frontiers in Cellular and Infection Microbiology.

                Article
                10.3389/fcimb.2013.00113
                3885817
                24409421
                3dfdf17b-edeb-479b-8ffd-f01044b34ba7
                Copyright © 2014 Wang, Kounatidis and Ligoxygakis.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 October 2013
                : 21 December 2013
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 179, Pages: 17, Words: 16400
                Categories
                Microbiology
                Review Article

                Infectious disease & Microbiology
                haemocytes,macrophage,innate immunity,haematopoiesis,plasmatocyte,tumor,inflammation

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