Article

Chemokine receptors and melanoma metastasis

Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
Journal of Dermatological Science (Impact Factor: 3.34). 12/2004; 36(2):71-8. DOI: 10.1016/j.jdermsci.2004.03.002
Source: PubMed

ABSTRACT Cancer metastasis is the end result of a complex series of biologic events that leads to the formation of clinically significant secondary tumors at distant sites. The sites of distant metastasis are not random since certain tumors show a tendency to develop metastases in specific organs. Human melanoma, for example, demonstrates frequent metastasis to brain, lungs, lymph nodes, and skin. Herein, we review the evidence that suggests that a limited number of chemokine receptors may play critical roles in determining organ-selective metastasis in melanoma by regulating diverse processes such as chemoattraction, adhesion, and survival. In particular, we describe roles for CC chemokine receptor 7 (CCR7) in lymph node metastasis, CXC chemokine receptor 4 (CXCR4) in pulmonary metastasis, and CCR10 in skin metastasis, using a mouse model of melanoma. Preliminary evidence in this preclinical model suggests that inhibiting the function of these receptors may decrease the ability of cancer cells to disseminate to other sites and/or block their ability to survive and form tumors. Therefore, manipulation of the chemokine network could have therapeutic potential in human malignancies.

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    • "It has also been shown that CCL2/CCR2 axis induces expression of SAA3/S100A8 which maintains vascular permeability regions via TLR4 and MD-2 receptors in tumor bearing premetastatic lung tissues [89]. Due to progress made over the past decades, it is now becoming clear that chemokines and their receptors may play a crucial role in different steps of tumorigenesis and metastasis [90] [91] [92]. "
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    ABSTRACT: Recently, there has been growing attention to the role of the tumor microenvironment (TME) in cancer growth, metastasis and emergence of chemotherapy resistance. Stromal and tumor cells make up the TME and interact with each other through a complex cross-talk manner. This interaction is facilitated by a variety of growth factors, cytokines, chemokines and S100 proteins. In this review, we focus on chemokines and their cognate receptors in regulating the tumorigenic process. Chemokines are cytokines that have chemotactic potential. Chemokine receptors are expressed on tumor cells and stromal cells. Chemokines and their cognate receptors modulate tumor growth and metastasis in a paracrine and autocrine manner. They play a major role in the modulation of stromal cell recruitment, angiogenic potential, cancer cell proliferation, survival, adhesion, invasion and metastasis to distant sites. In addition, a new class of calcium binding family S100 proteins has getting attention as they play significant roles in tumor progression and metastasis by modulating TME. Here, we highlight recent developments regarding the inflammatory chemokine/S100 proteins systems in the TME. We also focus on how chemokines/S100 proteins, through their role in the TME, modulate cancer cell ability to grow, proliferate, invade and metastasize to different organs. This review highlights the possibility of using the chemokine/chemokine receptor axis as a promising strategy in cancer therapy, the current difficulties in achieving this goal, and how it could be overcome for successful future therapeutic intervention. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Cancer letters 05/2015; 365(1). DOI:10.1016/j.canlet.2015.05.002 · 5.62 Impact Factor
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    • "Vol. 14, No. 12, 2012 IRF-8 Controls Melanoma Progression Mattei et al. 1227 regard to chemokine and chemokine receptors involved in metastasis and angiogenesis, we found CCR10, which promotes escape from host immunosurveillance and tumor growth [27] [28], expressed at high levels selectively in the CD45 − fraction of IRF-8–melanoma (Figure 5). Moreover , the angiostatic axis CXCL10/CXCR3 [29] [30] was significantly inhibited in IRF-8–melanoma but highly activated in WT-melanoma (Figure 5). "
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    • "Vol. 14, No. 12, 2012 IRF-8 Controls Melanoma Progression Mattei et al. 1227 regard to chemokine and chemokine receptors involved in metastasis and angiogenesis, we found CCR10, which promotes escape from host immunosurveillance and tumor growth [27] [28], expressed at high levels selectively in the CD45 − fraction of IRF-8–melanoma (Figure 5). Moreover , the angiostatic axis CXCL10/CXCR3 [29] [30] was significantly inhibited in IRF-8–melanoma but highly activated in WT-melanoma (Figure 5). "
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    ABSTRACT: The transcription factor interferon regulatory factor-8 (IRF-8) is crucial for myeloid cell development and immune response and also acts as a tumor suppressor gene. Here, we analyzed the role of IRF-8 in the cross talk between melanoma cells and tumor-infiltrating leukocytes. B16-F10 melanoma cells transplanted into IRF-8-deficient (IRF-8(-/-)) mice grow more rapidly, leading to higher numbers of lung metastasis, with respect to control animals. These events correlated with reduced dendritic cell and T cell infiltration, accumulation of myeloid-derived suppressor cells and a chemokine/chemokine receptor expression profile within the tumor microenvironment supporting tumor growth, angiogenesis, and metastasis. Noticeably, primary tumors developing in IRF-8(-/-) mice displayed a clear-cut inhibition of IRF-8 expression in melanoma cells. Injection of the demethylating agent 5-aza-2'-deoxycytidine into melanoma-bearing IRF-8(-/-) animals induced intratumoral IRF-8 expression and resulted in the re-establishment of a chemokine/ chemokine receptor pattern favoring leukocyte infiltration and melanoma growth arrest. Importantly, intrinsic IRF-8 expression was progressively down-modulated during melanoma growth in mice and in human metastatic melanoma cells with respect to primary tumors. Lastly, IRF-8 expression in melanoma cells was directly modulated by soluble factors, among which interleukin-27 (IL-27), released by immune cells from tumor-bearing mice. Collectively, these results underscore a key role of IRF-8 in the cross talk between melanoma and immune cells, thus revealing its critical function within the tumor microenvironment in regulating melanoma progression and invasiveness.
    Neoplasia (New York, N.Y.) 12/2012; 14(12):1223-35. DOI:10.1593/neo.121444 · 5.40 Impact Factor
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