Role of CX3CR1/CX3CL1 axis in primary and secondary involvement of the nervous system by cancer

CX3CL1 or Fractalkine is a peculiar chemokine that can exist either in a soluble form, like all the other chemokines, and as a cell membrane molecule. CX3CL1 is one of the most expressed chemokines in the central nervous system, where it regulates the communication between neurons, glia and microglia. CX3CR1-expressing microglia may have an important role in limiting tissue injury during inflammation and neuro-degeneration. Recent evidence has implicated CX3CL1 and its cognate receptor CX3CR1 in cancer. Tumors of neural origin (glioma, neuroblastoma) express CX3CR1 which is involved in the adhesion, transendothelial migration and mobilization of tumor cells. In addition, tumors of non-neural origin, like prostate, pancreas and breast carcinoma express high levels of the CX3CR1 receptor. As for other chemokine receptors, CX3CR1 expression is associated with increased migration and site specific dissemination. In pancreatic cancer, receptor expression is involved in the perineural invasion and dissemination of neoplastic cells along intra- and extra-pancreatic nerves. This peculiar route of tumor spread is used also by other carcinomas (e.g. prostate, head and neck) and may represent a target for therapeutic intervention.