Neuropilin: Handyman and Power Broker in the Tumor Microenvironment

  • Stephan NilandEmail author
  • Johannes A. Eble
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1223)


Neuropilin-1 and neuropilin-2 form a small family of transmembrane receptors, which, due to the lack of a cytosolic protein kinase domain, act primarily as co-receptors for various ligands. Performing at the molecular level both the executive and organizing functions of a handyman as well as of a power broker, they are instrumental in controlling the signaling of various receptor tyrosine kinases, integrins, and other molecules involved in the regulation of physiological and pathological angiogenic processes. In this setting, the various neuropilin ligands and interaction partners on various cells of the tumor microenvironment, such as cancer cells, endothelial cells, cancer-associated fibroblasts, and immune cells, are surveyed. The suitability of various neuropilin-targeting substances and the intervention in neuropilin-mediated interactions is considered as a possible building block of tumor therapy.


Cancer cell Endothelial cell Neuropilin interacting partners Neuropilin ligands Neuropilin signaling Semaphorin Tumor-penetrating peptides Tumor angiogenesis Tumor microenvironment Tumor stromal cell Vascular endothelial growth factor 



3′-Untranslated region


A disintegrin and metalloproteinase domain containing protein


A disintegrin and metalloproteinase with thrombospondin motifs




Protein kinase B


Anaplastic lymphoma kinase


Activin receptor-like kinase; serine/threonine-protein kinase receptor R3


Activin receptor-like kinase; TGF-β receptor 1


Bone morphogenetic protein


Rat/rapidly accelerated fibrosarcoma, isoform B


Cancer-associated fibroblasts


Cluster of differentiation


Carboxy-terminal end rule


Cancer stem cell

CUB domain

Cubilin homology domain


Discoidin domain receptor

Dlg domain

Discs large domain


Endothelial cell


Extracellular matrix


Epidermal growth factor (receptor)


Epithelial to mesenchymal transition


Erythropoietin-producing human hepatocellular (EPH) receptor A2


Endoplasmic reticulum


Erythroblastosis oncogene B


Extracellular-signal-regulated kinase


Focal adhesion kinase


Fibroblast growth factor (receptor)


Frizzled-related protein


G alpha interacting protein


GTPase activation protein


Globular head of complement factor C1q binding protein/receptor


Guanine nucleotide exchange factor


GAIP interacting protein, C-terminus


GIPC PDZ domain containing family member 1, synectin


Glioma-associated oncogene homolog 1


Glucose transporter 1 C-terminal binding protein


Human epidermal growth factor receptor 2


Hepatocyte growth factor (receptor)




Insulin-like growth factor 1 (IGF-1) receptor


Insulin-like growth factor-1 receptor-interacting protein 1


c-Jun N-terminal kinase


Kirsten rat sarcoma


L1 cell adhesion molecule


Laminin subunit γ2


Long noncoding RNA


Low-density lipoprotein receptor related protein 5

MAM domain



Mitogen-activated protein (kinase)


Mesenchymal-epithelial transition factor (MET) proto-oncogene




Matrix metalloproteinase


Neuropilin-1 interacting protein




CRK-associated substrate


Platelet-derived growth factor (receptor)


Postsynaptic density/discs large/zonula occludens-1


Phosphoinositide 3-kinase


Protein kinase C


Placenta growth factor (receptor)

PSD-95 domain

Postsynaptic density protein 95 domain


Phosphatase and tensin homolog


Protein tyrosine phosphatase μ


Rat sarcoma


Rho guanine nucleotide exchange factor 1


Receptor-type tyrosine kinase


Stress-activated protein kinase 1




Semaphorin 4C (SEMA4C)-interacting protein 1


sma(ll) and Daf-4 homolog


Soluble neuropilin




Synectin-binding GEF


Tumor-associated macrophage


Tumor endothelial cell


Tissue factor pathway inhibitor


Transforming growth factor-β (receptor)


Tyrosine kinase with immunoglobulin-like and EGF-like domains


Tax-interacting protein 2


Rapamycin-sensitive TOR complex 2


Regulatory T cell


Urokinase plasminogen activator


Vascular adhesion protein-1


Vascular endothelial growth factor (receptor)


Vasculogenic mimicry


Wnt inhibitory factor 1


Wingless-related integration site


Yes-associated protein 1

ZO-1 domain

Zonula occludens-1 domain



The author’s scientific work on NRP1 is financially supported by Deutsche Forschungs gemeinschaft (grant: SFB1009 A09).


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Institute of Physiological Chemistry and PathobiochemistryUniversity of MünsterMünsterGermany

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