title: Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth.
abstract: Mesenchymal stem cells (MSCs) have opposite effects on tumor growth, being able either to favor angiogenesis and tumor initiation or to inhibit progression of established tumors. Factors produced by MSCs within the tumor microenvironment may be relevant for their biological effects. Recent studies demonstrated that microvesicles (MVs) are an integral component of inter-cellular communication within the tumor microenvironment. In the present study, we evaluated whether MVs derived from human bone marrow MSCs may stimulate or inhibit in vitro and in vivo growth of HepG2 hepatoma, Kaposi's sarcoma, and Skov-3 ovarian tumor cell lines. We found that MVs inhibited cell cycle progression in all cell lines and induced apoptosis in HepG2 and Kaposi's cells and necrosis in Skov-3. The observed activation of negative regulators of cell cycle may explain these biological effects. In vivo intra-tumor administration of MVs in established tumors generated by subcutaneous injection of these cell lines in SCID mice significantly inhibited tumor growth. In conclusion, MVs from human MSCs inhibited in vitro cell growth and survival of different tumor cell lines and in vivo progression of established tumors.
authors.affiliation: Department of Internal Medicine, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bruno
authors.forename: Federica
authors.initials: F
authors.lastname: Collino
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Deregibus
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology / Q000648:ultrastructure*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D022162:Cytoplasmic Vesicles / Q000502:physiology* / Q000637:transplantation; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D016513:Mice, SCID; D009336:Necrosis; D009369:Neoplasms / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology; D012514:Sarcoma, Kaposi / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D017077:Culture Media, Conditioned