Differential Expression of Chemokine Receptors and their Roles in Cancer Imaging

Sridhar Nimmagadda

doi:10.3389/fonc.2012.00046

Abstract

Chemokine/chemokine receptor interactions play diverse roles in cell migration and homeostasis. Emerging evidence suggests that cancer cells co-opt chemokine networks for survival, proliferation, immune evasion, and metastasis. Most of the chemokine receptors are reported to be involved in tumor progression. Given their extensive implication in cancer progression, several chemokine receptor/ligand axes are considered as potential therapeutic targets. This review provides a survey of chemokine receptor expression in cancer and evaluates the potential of chemokine receptor imaging as a tool for molecular characterization of cancer.

Highlights

Chemokine/chemokine receptor interactions play key roles in cell trafficking in host defense mechanisms, in organogenesis, vasculogenesis, and tissue repair
A growing body of literature suggests that most chemokine receptors, as shown in Table 1, including CXCR2, CXCR3, CXCR4, CXCR7, and CCR7 play key roles in cancer cell survival, proliferation, homing, adhesion, tumor angiogenesis, and resistance to conventional and targeted therapies
In spite of high expression on tumor cells, downregulation of CXCR3 by siRNA, or inhibition by low molecular weight agents was not shown to have an effect on breast or melanoma tumor growth but rather influenced the metastatic ability of the cancer cells to the lungs and lymph nodes (LN) (Kawada et al, 2004)

Summary

INTRODUCTION

Chemokine/chemokine receptor interactions play key roles in cell trafficking in host defense mechanisms, in organogenesis, vasculogenesis, and tissue repair. A growing body of literature suggests that most chemokine receptors, as shown, including CXCR2, CXCR3, CXCR4, CXCR7, and CCR7 play key roles in cancer cell survival, proliferation, homing, adhesion, tumor angiogenesis, and resistance to conventional and targeted therapies. Both receptors are expressed on granulocytes, monocytes, and mast cells and on some CD8+ T cells and CD56+ natural killer (NK) cells (Chuntharapai et al, 1994) Functional effects of both the receptors are well characterized for the binding of the inflammatory ligand CXCL8 (IL8) than any other ligand (Waugh and Wilson, 2008). CXCR1 binds only CXCL8 with high affinity, whereas CXCR2 is known to bind all the ligands with high affinity (Waugh and Wilson, 2008) Both receptors have been shown to play important roles in tumor progression in several cancers. In advanced prostate cancer specimens, CXCR1, CXCR2, and CXCL8 expression were found to localize www.frontiersin.org

Chemokine receptor imaging

Tumor expression

Head and neck