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: 3.42). 12/2004; 36(2):71-8. DOI: 10.1016/j.jdermsci.2004.03.002
Source: PubMed


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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    • "Indeed, it has been shown that mouse melanoma B16F10 cells constitutively express CXCR3, and its ligands CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC induce cellular responses in vitro, such as actin polymerization, migration, invasion, and cell survival [12]. Moreover, the expression of several chemokine receptors has been associated with a greater risk of developing regional and distant metastases [7,8] as lymph node metastasis (CCR7 [13]; CCR10, [14]; CXCR3 and CXCR4; [15]), pulmonary metastasis (CXCR4) or skin metastasis (CCR10; [13]). The role in melanoma of the recently discovered CXCR7, which binds to CXCL11 and CXCL12 [16] is still not clear. "
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    ABSTRACT: Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival. In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues).WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed. Our results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface. Coexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis).
    BMC Cancer 02/2014; 14(1):118. DOI:10.1186/1471-2407-14-118 · 3.36 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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