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      Chemokines in tumor progression and metastasis

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          Abstract

          Chemokines play a vital role in tumor progression and metastasis. Chemokines are involved in the growth of many cancers including breast cancer, ovarian cancer, pancreatic cancer, melanoma, lung cancer, gastric cancer, acute lymphoblastic leukemia, colon cancer, non-small lung cancer and non-hodgkin's lymphoma among many others. The expression of chemokines and their receptors is altered in many malignancies and leads to aberrant chemokine receptor signaling. This review focuses on the role of chemokines in key processes that facilitate tumor progression including proliferation, senescence, angiogenesis, epithelial mesenchymal transition, immune evasion and metastasis.

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          Most cited references157

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          Distinct role of macrophages in different tumor microenvironments.

          Macrophages are prominent in the stromal compartment of virtually all types of malignancy. These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes.
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            Chemokine signaling via the CXCR2 receptor reinforces senescence.

            Cells enter senescence, a state of stable proliferative arrest, in response to a variety of cellular stresses, including telomere erosion, DNA damage, and oncogenic signaling, which acts as a barrier against malignant transformation in vivo. To identify genes controlling senescence, we conducted an unbiased screen for small hairpin RNAs that extend the life span of primary human fibroblasts. Here, we report that knocking down the chemokine receptor CXCR2 (IL8RB) alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Conversely, ectopic expression of CXCR2 results in premature senescence via a p53-dependent mechanism. Cells undergoing OIS secrete multiple CXCR2-binding chemokines in a program that is regulated by the NF-kappaB and C/EBPbeta transcription factors and coordinately induce CXCR2 expression. CXCR2 upregulation is also observed in preneoplastic lesions in vivo. These results suggest that senescent cells activate a self-amplifying secretory network in which CXCR2-binding chemokines reinforce growth arrest.
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              Chemokines: a new classification system and their role in immunity.

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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                December 2013
                9 November 2013
                : 4
                : 12
                : 2171-2185
                Affiliations
                1 The Brain Tumor Center, The University of Chicago, Chicago, Illinois, USA
                Author notes
                Correspondence to: Maciej S. Lesniak, mlesniak@ 123456surgery.bsd.uchicago.edu
                Article
                10.18632/oncotarget.1426
                3926818
                24259307
                c76b5517-7052-4640-b3d2-6ac1d84519f2
                Copyright: © 2013 Sarvaiya et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 September 2013
                : 8 November 2013
                Categories
                Review

                Oncology & Radiotherapy
                chemokines,chemokine receptors,cancer,metastasis
                Oncology & Radiotherapy
                chemokines, chemokine receptors, cancer, metastasis

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