HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-102855v1 22/9/3358    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ristorcelli, E. Articles by Verine, A. PubMed PubMed Citation Articles by Ristorcelli, E. Articles by Verine, A.

Human tumor nanoparticles induce apoptosis of pancreatic cancer cells

INSERM UMR 911; Aix-Marseille Université, Marseille, France

¹ Corresponding author: Faculté de Médecine, 27 Bld Jean Moulin, 13385 Marseille Cedex 05, France. E-mail: dominique.lombardo{at}medecine.univ-mrs.fr

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) -3β activation and decreased pyruvate dehydrogenase activity. In nanoparticle-treated cells, PTEN formed complexes with actin, β-catenin, and GSK-3β. Thus, β-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.—Ristorcelli, E., Beraud, E., Verrando, P., Villard, C., Lafitte, D., Sbarra, V., Lombardo, D., Verine, A. Human tumor nanoparticles induce apoptosis of pancreatic cancer cells.

Key Words: exosomes • cell death • proliferation