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.
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.
Frankel
Paul
P
Department of Medicine, Centre for Cardiovascular Biology and Medicine, University College London, 5 University Street, London WC1E 6JJ, UK. p.frankel@ucl.ac.uk
Pellet-Many
Caroline
C
Lehtolainen
Pauliina
P
D'Abaco
Giovanna M
GM
Tickner
Michelle L
ML
Cheng
Lili
L
Zachary
Ian C
IC
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates / Q000502:physiology*; D050719:Crk-Associated Substrate Protein / Q000502:physiology*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D039942:Neuropilin-1 / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine
C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D039942:Neuropilin-1; D002809:Chondroitin Sulfates