Chondroitin sulphate-modified neuropilin 1 is expressed in human tumour cells and modulates 3D invasion in the U87MG human glioblastoma cell line through a p130Cas-mediated pathway

• Published in: EMBO reports Vol. 9; no. 10; pp. 983 - 989
• Main Authors: Frankel, Paul, Pellet-Many, Caroline, Lehtolainen, Pauliina, D'Abaco, Giovanna M, Tickner, Michelle L, Cheng, Lili, Zachary, Ian C
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2008; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Amino Acid Sequence; Animals; Brain cancer; Cell Line, Tumor; Cellular biology; Chondroitin Sulfates - physiology; Crk-Associated Substrate Protein - physiology; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; growth factors; Humans; Kinases; metastasis; Mice; Molecular biology; Molecular Sequence Data; Neoplasm Invasiveness; Neuropilin-1 - biosynthesis; Neuropilin-1 - genetics; proteoglycan; Rats; RNA Interference; Scientific Report; Signal Transduction - physiology; Swine; Tumors; VEGF
• ISSN: 1469-221X; 1469-3178; 1469-221X
• DOI: 10.1038/embor.2008.151

Neuropilin 1 (NRP1), a non‐tyrosine kinase receptor for vascular endothelial growth factor and class 3 Semaphorins, is highly expressed in many human tumour cell lines, but its function is poorly understood. Here, we describe the expression of a new chondroitin sulphate‐modified NRP1 (NRP1‐CS) in human tumour cell lines. Expression of a non‐modifiable NRP1 mutant (S612A) in U87MG human glioma cells results in enhanced invasion in three dimensions (3D), whereas wild‐type NRP1 has no effect. Furthermore, the S612A NRP1 cells show a significant increase in p130Cas tyrosine phosphorylation compared with control and wild‐type NRP1 cells. Silencing of p130Cas in S612A NRP1 cells resulted in a loss of increased invasive phenotype. Interestingly, p130Cas silencing does not inhibit basal 3D invasion, but leads to a mesenchymal to amoeboid transition. Biopsies from both low‐ and high‐grade human gliomas show strong expression of NRP1, and little expression of NRP1‐CS. Our data establish distinct roles for NRP1 and NRP1‐CS in modulating a new NRP1‐p130Cas signalling pathway contributing to glioblastoma cell invasion in 3D.