Neuropilins, as Relevant Oncology Target: Their Role in the Tumoral Microenvironment

Abstract

Angiogenesis is one of the key mechanisms involved in tumor growth and metastatic dissemination. The vascular endothelial growth factor (VEGF) and its receptors (VEGFR) represent one of the major signaling pathways which mediates angiogenesis. The VEGF/VEGFR axis was intensively targeted by monoclonal antibodies or by tyrosine kinase inhibitors to destroy the tumor vascular network. By inhibiting oxygen and nutrient supply, this strategy was supposed to cure cancers. However, despite a lengthening of the progression free survival in several types of tumors including colon, lung, breast, kidney, and ovarian cancers, modest improvements in overall survival were reported. Anti-angiogenic therapies targeting VEGF/VEGFR are still used in colon and ovarian cancer and remain reference treatments for renal cell carcinoma. Although the concept of inhibiting angiogenesis remains relevant, new targets need to be discovered to improve the therapeutic index of anti-VEGF/VEGFR. Neuropilin 1 and 2 (NRP1/2), initially described as neuronal receptors, stimulate angiogenesis, lymphangiogenesis and immune tolerance. Moreover, overexpression of NRPs in several tumors is synonymous of patients' shorter survival. This article aims to overview the different roles of NRPs in cells constituting the tumor microenvironment to highlight the therapeutic relevance of their targeting.

miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

“…The family includes two homologous isoforms, Neuropilin-1 and Neuropilin-2, encoded by distinct genes on different chromosomes (10p12 and 2q34, respectively) [ 6 ]. Both isoforms are upregulated in a number of clinical disorders, including cancer, where they increase the oncogenic activities of malignant cells by promoting survival, inducing angiogenesis and lymphangiogenesis, and contribute to therapy resistance [ 7 ]. Neuropilin-1 has been shown to regulate the endothelium-dependent inflammatory responses at the level of the blood–brain barrier [ 8 ].…”

miR-24 targets SARS-CoV-2 co-factor Neuropilin-1 in human brain microvascular endothelial cells: Insights for COVID-19 neurological manifestations

“…The family includes two homologous isoforms, Neuropilin-1 and Neuropilin-2, encoded by distinct genes on different chromosomes (10p12 and 2q34, respectively) [6]. Both isoforms are upregulated in a number of clinical disorders, including cancer, where they increase the oncogenic activities of malignant cells by promoting survival, inducing angiogenesis and lymphangiogenesis and contribute to therapy resistance [7]. Neuropilin-1 has been shown to regulate the endothelium-dependent in ammatory responses at the level of the blood-brain barrier [8].…”

Loss of neuropilin1 inhibits liver cancer stem cells population and blocks metastasis in hepatocellular carcinoma via epithelial-mesenchymal transition

“…Accumulating evidences show that NRP1 is a tumor-promoting factor, up-regulated in a variety of tumors, promoting proliferation and metastasis [24]. From the perspective of NRP1 promoting the proportion of surface markers of liver CSCs, our research inferred that NRP1 is related to the clinical features of HCC.…”