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      Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation

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          Abstract

          Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive cancer. The tumor tissue, which shows an active angiogenesis, is composed of neoplastic and stromal cells, and an abundant inflammatory infiltrate. Angiogenesis is important to support tumor growth, while infiltrating cells contribute to the tumor microenvironment through the secretion of growth factors, cytokines and chemokines, important molecules in the progression of the disease. Chemokines are important in development, activation of the immune response, and physiological angiogenesis. Chemokines have emerged as important regulators in the pathophysiology of cancer. These molecules are involved in the angiogenesis/angiostasis balance and in the recruitment of tumor infiltrating hematopoietic cells. In addition, chemokines promote tumor cell survival, as well as the directing and establishment of tumor cells to metastasis sites. The findings summarized here emphasize the central role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in the inflammatory process of NSCLC angiogenesis.

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          Most cited references154

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          Chemokines: a new classification system and their role in immunity.

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            Endothelial cell migration during angiogenesis.

            Endothelial cell migration is essential to angiogenesis. This motile process is directionally regulated by chemotactic, haptotactic, and mechanotactic stimuli and further involves degradation of the extracellular matrix to enable progression of the migrating cells. It requires the activation of several signaling pathways that converge on cytoskeletal remodeling. Then, it follows a series of events in which the endothelial cells extend, contract, and throw their rear toward the front and progress forward. The aim of this review is to give an integrative view of the signaling mechanisms that govern endothelial cell migration in the context of angiogenesis.
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              International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors.

              Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52:145-176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U.S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2015
                7 August 2015
                : 6
                : 10
                : 938-952
                Affiliations
                1. Department of Biochemistry Research, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico.
                2. Laboratory of Research on Rheumatic Diseases, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico.
                3. Department of Comparative Biology, Faculty of Sciences, National Autonomous University of Mexico, Mexico City, Mexico.
                4. Laboratory of Research on Genomics, Genetics and Bioinformatics. Tower of Haemato-oncology, Children´s Hospital of Mexico “Federico Gomez”, Mexico City, Mexico.
                Author notes
                ✉ Corresponding author: Department of Biochemistry Research, National Institute of Respiratory Diseases “Ismael Cosío Villegas”, Mexico City, Mexico. Calzada de Tlalpan 4502, Tlalpan, Ciudad de México, D.F. 14080, México. Phone +52 (55) 5487 1705; E-mail: selma.rivas@ 123456iner.gob.mx .

                Competing Interests: No competing interests were disclosed.

                Article
                jcav06p0938
                10.7150/jca.12286
                4543754
                26316890
                ac2ebcdb-014d-4e66-bf51-f8904b138c28
                © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                : 30 March 2015
                : 23 June 2015
                Categories
                Review

                Oncology & Radiotherapy
                chemokines,cytokines,angiogenesis,inflammation,non-small cell lung cancer.
                Oncology & Radiotherapy
                chemokines, cytokines, angiogenesis, inflammation, non-small cell lung cancer.

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