title: Acquisition of new tumor cell properties by MSC-derived exosomes.
abstract: Interaction between multi-functional mesenchymal stroma/stem cells (MSC) and human tumor cells involves the exchange of biological material via extracellular vesicles including exosomes. Protein analysis of MSC-derived exosomes demonstrated the presence of MMP-2 and MSC-specific markers including CD90 and ecto-5'-nucleotidase (CD73). Incubation of tumor cells with these membranous particles revealed a rapid uptake of MSC-released microvesicles whereby breast cancer cells incorporated ~19% and SCCOHT-1 cells representing a rare type of small cell ovarian cancer assimilated ~28% of available exosomes within 24 h. This interaction was accompanied by functional alterations of tumor cell properties during integration of exosomal content from MSC. Indeed, exosome-associated MMP-2 exhibited functional enzyme activity and MCF-7 breast cancer cells with undetectable MMP-2 protein acquired expression of this enzyme and corresponding gelatinase functionality after stimulation with MSC-derived exosomes. Similar effects were observed in SCCOHT-1 cells during culture in the presence of MSC-derived exosomes which enabled new metabolic activities in this tumor cell type. Together, these findings demonstrated that the internalization of MSC-derived exosomes was associated with the acquisition of new tumor cell properties by altering cellular functionalities and providing the capability to re-organize the tumor microenvironment.
authors.affiliation: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Vesna
authors.initials: V
authors.lastname: Bucan
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Baehre
authors.affiliation: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: von der Ohe
authors.affiliation: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Otte
authors.affiliation: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics; D059016:Tumor Microenvironment
chemical_list: D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2