The role of neuropilins in cancer

Abstract

Neuropilins are multifunctional non -tyrosine kinase receptors that bind to class 3 semaphorins and vascular endothelial growth factor. NRP-1 and NRP-2 were first identified for their key role in mediating axonal guidance in the developing nervous system through their interactions with class 3 semaphorins. Growing evidence supports a critical role for these receptors in tumor progression. Neuropilin expression is up-regulated in multiple tumor types, and correlates with tumor progression and prognosis in specific tumors. Neuropilins may indirectly mediate effects on tumor progression by affecting angiogenesis or directly through effects on tumor cells. This article reviews emerging evidence for the role of neuropilins in tumor biology. The therapeutic implications of these data are far-reaching and suggest that neuropilin-targeted interventions may be useful as a component of antineoplastic therapy.

Overexpression of VEGF189 in breast cancer cells induces apoptosis via NRP1 under stress conditions

“…11,12,14,[22][23][24][25][26] As NRP1 is widely expressed in our derived MDA-MB-231 clones, the effects of VEGF isoforms on survival/apoptosis may involve NRP1. The silencing of NRP1 decreased the apoptosis of clones overexpressing VEGF189 under serum starvation or doxorubicin treatment, and resulted in more necrosis in both conditions than observed for shCtl-transfected V189 clones.…”

“…20,21 NRP1 is expressed at high levels in several tumor cells, where it has been implicated in cell migration and survival. 11,12,[22][23][24][25][26][27] Recently, our group showed that VEGF189 binds to NRP1, 10 in addition to VEGF165. However, the role of VEGF189-NRP1 association in survival has not been elucidated.…”

Transtumoral targeting enabled by a novel neuropilin-binding peptide

“…Tumors examined 1 h after the injection of FAM-tLyP-1 were strongly fluorescent under blue light (Figure 5a). Normal tissues, which express NRP1 at lower levels than tumors (Ellis, 2006;Guttmann-Raviv et al, 2006;Bagri et al, 2009), were negative, with the exception of the kidneys, which reflects the clearance of the peptide through this organ. A control peptide, FAM-ARALPSQRSR (Laakkonen et al, 2002), did not accumulate in the 4T1 tumors.…”

The Role of micro RNAs in Breast Cancer Metastasis: Preclinical Validation and Potential Therapeutic Targets

“…Wingless/integrated1 (Wnt1) and neuropilin-1 (NRP1) were identified as direct targets for miR-148a (94). Wnt-1 induced Wnt signaling can promote EMT and metastasis (95,96) and NRP1 functions as mediator of cell growth, survival and metastasis (97,98). miR-148b: In a retrospective study, miR-148b and additional 15 miRs were found to be associated with relapse in BC patients (99).…”