Human tumor nanoparticles induce apoptosis of pancreatic cancer cells
- 29 May 2008
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 22 (9), 3358-3369
- https://doi.org/10.1096/fj.07-102855
Abstract
Exosomes are vesicles secreted by most hematopoietic cells on fusion of multivesicular endosomes with the plasma membrane. Many studies have reported that exosomes may also be released by tumor cells. Exosomes are believed to play an antitumor role through immune cells. We asked whether tumor exosomes have biological activities on tumor cells. We report that human pancreatic tumor nanoparticles, exosome-like as characterized by proteomic analyses and rich in lipid rafts, decreased tumor cell proliferation. Nanoparticles increased Bax and decreased Bcl-2 expressions. Caspase-3 and -9 but not caspase-8 inhibitors impaired apoptosis, which implicates the mitochondria apoptotic pathway. The ceramide-sphingomyelin apoptotic pathway was inoperative. Moreover, nanoparticles induced phosphatase and tensin homolog (PTEN) and glycogen synthase kinase (GSK) -3beta activation and decreased pyruvate dehydrogenase activity. In nanoparticle-treated cells, PTEN formed complexes with actin, beta-catenin, and GSK-3beta. Thus, beta-catenin may no longer be available to activate the survival pathway. Nanoparticles triggered the down-regulation of cyclin D1 and poly(ADP-ribose) polymerase. Hence, nanoparticles counteracted the constitutively activated phosphatidylinositol 3-kinase/Akt survival pathway to drive tumor cells toward apoptosis. Our study provides the first evidence of an apoptotic function of tumor-derived nanoparticles on tumor cells. We propose a new role for nanoparticles, i.e., as signal carriers for interaction between cells, which may have implications in physiopathological situations.Keywords
Funding Information
- Institut National de la Santé et de la Recherche Médicale
This publication has 52 references indexed in Scilit:
- Emission of membrane vesicles: roles in complement resistance, immunity and cancerSpringer Seminars in Immunopathology, 2005
- Dendritic Cell-Derived Exosomes as Cell-Free Peptide-Based VaccinesCritical Reviews in Immunology, 2005
- Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancerInternational Journal of Cancer, 2004
- Exosome Secretion: The Art of Reutilizing Nonrecycled Proteins?Traffic, 2004
- Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organizationBiochemical Journal, 2004
- Exosomes as Potent Cell-Free Peptide-Based Vaccine. I. Dendritic Cell-Derived Exosomes Transfer Functional MHC Class I/Peptide Complexes to Dendritic CellsPublished by The American Association of Immunologists ,2004
- Proteomic and Biochemical Analyses of Human B Cell-derived ExosomesPublished by Elsevier BV ,2003
- Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-primingNature Medicine, 2001
- Characteristics of the Interaction between Hsc70 and the Transferrin Receptor in Exosomes Released during Reticulocyte MaturationPublished by Elsevier BV ,2001
- Capacity of mouse mast cells to prime T cells and to induce specific antibody responsesin vivoImmunology, 2001