Chemokine receptors and melanoma metastasis
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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ABSTRACT: G-protein-coupled receptors (GPCR) are the largest family of receptors with over 500 members. Evaluation of GPCR gene expression in primary human tumors identified over-expression of GPCR in several tumor types. Analysis of cancer samples in different disease stages also suggests that some GPCR may be involved in early tumor progression and others may play a critical role in tumor invasion and metastasis. Currently, >50% of drug targets to various human diseases are based on GPCR. In this review, the relationships between several GPCR and melanoma development and/or progression will be discussed. Finally, the possibility of using one or more of these GPCR as therapeutic targets in melanoma will be summarized.Pigment Cell & Melanoma Research 05/2008; 21(4):415-28. DOI:10.1111/j.1755-148X.2008.00478.x · 5.64 Impact Factor
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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; DOI:10.1016/j.canlet.2015.05.002 · 5.02 Impact Factor
- Surgery 06/2014; 155(6). DOI:10.1016/j.surg.2014.02.006 · 3.11 Impact Factor