Journal article
Podoplanin is a component of extracellular vesicles that reprograms cell-derived exosomal proteins and modulates lymphatic vessel formation
P Carrasco-Ramírez, DW Greening, G Andrés, SK Gopal, E Martín-Villar, J Renart, RJ Simpson, M Quintanilla
Oncotarget | Published : 2016
Abstract
Podoplanin (PDPN) is a transmembrane glycoprotein that plays crucial roles in embryonic development, the immune response, and malignant progression. Here, we report that cells ectopically or endogenously expressing PDPN release extracellular vesicles (EVs) that contain PDPN mRNA and protein. PDPN incorporates into membrane shed microvesicles (MVs) and endosomal-derived exosomes (EXOs), where it was found to colocalize with the canonical EV marker CD63 by immunoelectron microscopy. We have previously found that expression of PDPN in MDCK cells induces an epithelial-mesenchymal transition (EMT). Proteomic profiling of MDCK-PDPN cells compared to control cells shows that PDPN-induced EMT is ass..
View full abstractGrants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Manuel Izquierdo from the Instituto de Investigaciones Biomedicas Alberto Sols for his kind help during our first steps into the EV field. We also thank Lucia Montero from the same Institute for her help in searching 3' UTR PDPN sequences similar to the consensus sequence reported for transcripts enriched in EVs, Francisco Sanchez-Madrid from the Hospital Universitario La Princesa for his generous gift of CD44 antibody, Virginia Albinana and Luisa Botella from the Centro de Investigaciones Biologicas for their help with the angiogenesis assay, Hector Peinado from the Centro Nacional de Investigaciones Oncologicas for his generous gift of HLECs, and Milagros Guerra from the Electron Microscopy Unit at Centro de Biologia Molecular Severo Ochoa for skillful technical assistance. We acknowledge the La Trobe University-Comprehensive Proteomics Platform for providing infrastructure and expertise for Capability A: Protein Identification & Quantitation. This work was supported by grants SAF2013-46183-R from the Spanish Ministry of Economy and Competitiveness and S2010/BMD-2359 (SkinModel) from the Community of Madrid (to MQ). Further support from the National Health and Medical Research Council of Australia Program, grant 487922 and project grant 1057741 (to RJS). PC-R is funded by the Spanish FPI (Formacion de Personal Investigador) program. SKG is supported by La Trobe University Postgraduate Scholarship, Australia. EM-V is the recipient of a postdoctoral research contract from the scientific foundation of AECC (Asociacion Espanola Contra el Cancer).