SHARPENING

Role of CX3CR1/CX3CL1 axis in primary and secondary involvement of the nervous
system by cancer
Federica Marchesi a, Marco Locatelli b, Graziella Solinas a, Marco Erreni a,
Paola Allavena a, Alberto Mantovani a,c,⁎


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. 

 Fig. 1. CX3CR1 in primary tumors of the nervous system and metastasis. Different tumors expressing CX3CR1 are represented, together with the organs or tissues which are the site of secondary localization. 

Fig. 2. Perineural invasion in pancreatic adenocarcinoma. 
(A) Histological section of pancreatic cancer (T) invading the perineural space (N, circled section).
Immunoreactivity with an anti-CX3CR1 depicts pancreatic tumor cells (magnification 40×).
(B) Schematic representation of some of the molecular mechanisms involved in perineural invasion. 
A nerve inside the pancreas developing a tumor is represented. 
Tumor cells adhere to neural cells, infiltrating the perineural space. 
Molecules involved in this interaction include the chemokine Fractalkine/Neurotactin (CX3CL1) expressed by neurons and its receptor CX3CR1 on tumor cells. 
Neurotropins secreted by neural and tumor cells sustain growth and survival of both intratumoral nerves and cancer cells.