title: Proteomic signatures of extracellular vesicles secreted by nonmineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth.
abstract: Beyond forming bone, osteoblasts play pivotal roles in various biologic processes, including hematopoiesis and bone metastasis. Extracellular vesicles (EVs) have been implicated in intercellular communication via transfer of proteins and nucleic acids between cells. We focused on the proteomic characterization of nonmineralizing (NMOBs) and mineralizing (MOBs) human osteoblast (SV-HFOs) EVs and investigated their effect on human prostate cancer (PC3) cells by microscopic, proteomic, and gene expression analyses. Proteomic analysis showed that 97% of the proteins were shared among NMOB and MOB EVs, and 30% were novel osteoblast-specific EV proteins. Label-free quantification demonstrated mineralization stage-dependent 5-fold enrichment of 59 and 451 EV proteins in NMOBs and MOBs, respectively. Interestingly, bioinformatic analyses of the osteoblast EV proteomes and EV-regulated prostate cancer gene expression profiles showed that they converged on pathways involved in cell survival and growth. This was verified by in vitro proliferation assays where osteoblast EV uptake led to 2-fold increase in PC3 cell growth compared to cell-free culture medium-derived vesicle controls. Our findings elucidate the mineralization stage-specific protein content of osteoblast-secreted EVs, show a novel way by which osteoblasts communicate with prostate cancer, and open up innovative avenues for therapeutic intervention.
authors.affiliation: Department of Internal Medicine and Erasmus MC Stem Cell and Regenerative Medicine Institute.
authors.forename: Jess
authors.initials: J
authors.lastname: Morhayim
authors.affiliation: Department of Internal Medicine and Erasmus MC Stem Cell and Regenerative Medicine Institute.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van de Peppel
authors.affiliation: Proteomics Center, and.
authors.forename: Jeroen A A
authors.initials: JA
authors.lastname: Demmers
authors.affiliation: Department of Internal Medicine and Erasmus MC Stem Cell and Regenerative Medicine Institute.
authors.forename: Gulistan
authors.initials: G
authors.lastname: Kocer
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands; and.
authors.forename: Alex L
authors.initials: AL
authors.lastname: Nigg
authors.affiliation: Department of Internal Medicine and Erasmus MC Stem Cell and Regenerative Medicine Institute.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Driel
authors.affiliation: Department of Basic Pathology, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Chiba
authors.affiliation: Department of Internal Medicine and Erasmus MC Stem Cell and Regenerative Medicine Institute, j.vanleeuwen@erasmusmusmc.nl.
authors.forename: Johannes P
authors.initials: JP
authors.lastname: van Leeuwen
mesh_terms: D002113:Calcification, Physiologic / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D040901:Proteomics; D059016:Tumor Microenvironment
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins
keywords: bioactivity; intercellular communication; prostate cancer; protein cargo