PMID- 20651071 OWN - NLM STAT- MEDLINE DCOM- 20101206 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 116 IP - 17 DP - 2010 Oct 28 TI - ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion. PG - 3219-26 LID - 10.1182/blood-2010-01-265611 [doi] AB - ATP, which has an important proinflammatory action as danger signal, induces the semimaturation of dendritic cells (DCs) that can be associated with immune tolerance. We identified epidermal growth factor receptor ligands as target genes of ATPgammaS, a slowly hydrolyzed ATP derivative, by a gene profiling approach in DCs. Amphiregulin was the most highly up-regulated gene in response to ATPgammaS. Human monocyte-derived DCs and mouse bone marrow-derived DCs released amphiregulin (AREG) after purinergic receptor activation, with a contribution of P2Y(11) and A(2B) receptor, respectively. Supernatants of LPS+ATPgammaS-stimulated DCs induced smooth muscle cell and Lewis Lung Carcinoma (LLC) cell growth in vitro. The coinjection of LPS+ATPgammaS-stimulated DCs or their supernatants with LLC cells increased tumor weight in mice compared with LPS-treated DCs. The preincubation of LPS+ATPgammaS-treated DC supernatants with an anti-AREG blocking antibody inhibited their positive effect on smooth muscle cell density and tumor growth. The present study demonstrates for the first time that DCs can be a source of AREG. ATP released from tumor cells might exert a tumorigenic action by stimulating the secretion of AREG from DCs. Antagonists of purinergic receptors expressed on DCs and anti-AREG blocking antibodies could have a therapeutic potential as antitumor agents. FAU - Bles, Nathalie AU - Bles N AD - Institute of Interdisciplinary Research, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universite Libre de Bruxelles, 808 Route de Lennik, Brussels, Belgium. FAU - Di Pietrantonio, Larissa AU - Di Pietrantonio L FAU - Boeynaems, Jean-Marie AU - Boeynaems JM FAU - Communi, Didier AU - Communi D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100722 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (EGF Family of Proteins) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - 35094-46-3 (adenosine 5'-O-(3-thiotriphosphate)) RN - 62229-50-9 (Epidermal Growth Factor) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/analogs & derivatives/*immunology MH - Amphiregulin MH - Animals MH - Bone Marrow Cells/cytology MH - Carcinoma, Lewis Lung/genetics/*immunology/pathology MH - Cell Line, Tumor MH - Cell Proliferation MH - Dendritic Cells/*immunology/metabolism/*pathology MH - EGF Family of Proteins MH - Epidermal Growth Factor/genetics MH - Gene Expression Regulation, Neoplastic MH - Glycoproteins/genetics/*immunology MH - Humans MH - Intercellular Signaling Peptides and Proteins/genetics/*immunology MH - Lipopolysaccharides/immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/immunology MH - Myocytes, Smooth Muscle/cytology MH - Up-Regulation EDAT- 2010/07/24 06:00 MHDA- 2010/12/14 06:00 CRDT- 2010/07/24 06:00 PHST- 2010/07/24 06:00 [entrez] PHST- 2010/07/24 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] AID - S0006-4971(20)31186-1 [pii] AID - 10.1182/blood-2010-01-265611 [doi] PST - ppublish SO - Blood. 2010 Oct 28;116(17):3219-26. doi: 10.1182/blood-2010-01-265611. Epub 2010 Jul 22.