CXCR4 and neoplasm: For instance, in PDAC, upregulated CCR7 and CXCR4 on tumor cells can promote lymph node invasion through binding to CCL21 and CXCL12 on lymphatic endothelium (99), whereas perineural invasion can involve axon guidance pathways (e.g., SEMA3D/PLXND1 and ROBO/SLIT2) and neurotrophic signals (e.g., GDNF/RET, NGF, and β-adrenergic signaling) shared between tumor cells and nerves (100–102).