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Proteomic signatures of extracellular vesicles secreted by nonmineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth
Author(s) -
Morhayim Jess,
Peppel Jeroen,
Demmers Jeroen A. A.,
Kocer Gulistan,
Nigg Alex L.,
Driel Marjolein,
Chiba Hideki,
Leeuwen Johannes P.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-261404
Subject(s) - osteoblast , microbiology and biotechnology , cell growth , extracellular vesicle , chemistry , extracellular , proteome , cell , biology , microvesicles , in vitro , biochemistry , gene , microrna
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.—Morhayim, J., van de Peppel, J., Demmers, J. A. A., Kocer, G., Nigg, A. L., van Driel, M., Chiba, H., van Leeuwen, J. P., Proteomic signatures of extracellular vesicles secreted by nonmineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth. FASEB J. 29, 274–285 (2015). www.fasebj.org