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Human tumor nanoparticles induce apoptosis of pancreatic cancer cells
Author(s) -
Ristorcelli Elodie,
Beraud Evelyne,
Verrando Patrick,
Villard Claude,
Lafitte Daniel,
Sbarra Véronique,
Lombardo Dominique,
Verine Alain
Publication year - 2008
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.07-102855
Subject(s) - microvesicles , microbiology and biotechnology , tensin , apoptosis , chemistry , exosome , cancer research , pten , ceramide , protein kinase b , signal transduction , pi3k/akt/mtor pathway , biology , biochemistry , microrna , gene
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. FASEB J. 22, 3358–3369 (2008)