Therapeutic potential of fractalkine: a novel approach to metastatic colon cancer

Fractalkine is involved in the pathogenesis of different types of cancer and in various clinical disease states Several experimental approaches have shown that a variety of chemokines have anti-tumour activity either by chemoattracting natural killer cells, monocytes and macrophages, or by accumulating dendritic cells.1 Accumulating evidence has shown that fractalkine (CX3CL1), the unique member of the CX3C chemokine subfamily, is involved in the pathogenesis of different types of cancer2,3 and in various clinical disease states beyond cancer, such as atherosclerosis, glomerulonephritis, rheumatoid arthritis, HIV disease and sepsis.4–6 In contrast with other chemokines, fractalkine exists in two forms, each mediating distinct biological actions.7 The membrane-anchored protein, which is expressed primarily on the endothelium, serves as an adhesion protein promoting the retention of monocytes and T cells.8 The soluble form originates from extracellular proteolysis by proteases, such as tumour necrosis factor-α converting enzyme (also known as ADAM17) and ADAM10.9 The secreted form resembles more a conventional chemokine and strongly induces chemotaxis and causes migration of natural killer cells, cytotoxic T lymphocytes and macrophages. Both chemotaxis and adhesion are mediated by the G protein-coupled receptor CX3CR1,10 which is present on natural killer cells, CD14+ monocytes and on some subpopulations of T cells. In a variety of pathological conditions, fractalkine …