Table 1.

Molecules involved in PNI.

Class of Molecules	Molecule	Role in PNI	Refs
Axonal guidance molecules	SLIT2–ROBO	Increased expression correlate with PNI and metastasis	[80,84]
Interleukin	LIF	Secreted by CAFs, increases neural plasticity and PNI	[89]
Chemokines and receptors	CCL2–CCR2	Recruits TAMs to cancer site promoting PNI via GDNF–RET signaling	[56,115,116,117,118]
	CXCR1–CX3CL1	Increases PNI and promotes cancer–nerve adhesion	[20,121,122,123]
Neurotrophinsand receptors	NGF–TrkA/p75NTR	Increases growth, proliferation and nerve–cancer affinity	[7,18,51,116,124,125,126,127,128,129,130,131,132,133,134,135,136]
	BDNF–TrkB	Increases in vitro proliferation; linked to metastasis	[137,138,139]
	NT3–TrkC	Increases cancer invasiveness, possible role in pain generation	[124,125,140,141]
GDNF family and receptors	GDNF–GFRα1–RET	Increases PNI; TAMs promote PNI through GDNF secretion	[2,64,83,142,143,144]
	Neurturin–GFRα2	Increased expression correlates to enhanced PNI	[128,145]
	Artemin–GFRα3	Promotes cancer migration and PNI	[146,147,148]
Cellular adhesion molecules	NCAM	Reduces cell—cell adhesion; increased expression contributes to PNI and metastasis	[92,149,150,151]
	L1CAM	Mediates homotipic interactions between cancer and nerve increasing PNI; upregulates MMP2–9 expression facilitating cancer progression	[152,153,154,155,156]
	MUC1	Increased levels promote cancer adhesion to nerves and metastasis	[88,157,158,159,160,161,162]
MMPs	MMP2–9	Increases PDAC aggressiveness	[163,164,165]