BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

被引：85

作者：

Rosati, Alessandra ^{[1
,2
]}

Basile, Anna ^{[1
,2
]}

D'Auria, Raffaella ^{[1
,3
]}

d'Avenia, Morena ^{[1
]}

De Marco, Margot ^{[1
]}

Falco, Antonia ^{[1
,3
]}

Festa, Michelina ^{[1
,3
]}

Guerriero, Luana ^{[1
,3
]}

Iorio, Vittoria ^{[1
,2
]}

Parente, Roberto ^{[1
]}

Pascale, Maria ^{[1
,3
]}

Marzullo, Liberato ^{[1
,2
]}

Franco, Renato ^{[4
]}

Arra, Claudio ^{[5
]}

Barbieri, Antonio ^{[5
]}

Rea, Domenica ^{[5
]}

Menichini, Giulio ^{[6
]}

Hahne, Michael ^{[7
]}

Bijlsma, Maarten ^{[8
]}

Barcaroli, Daniela ^{[9
]}

Sala, Gianluca ^{[9
]}

di Mola, Fabio Francesco ^{[10
]}

di Sebastiano, Pierluigi ^{[10
]}

Todoric, Jelena ^{[11
,12
]}

Antonucci, Laura ^{[11
,12
]}

Corvest, Vincent ^{[13
]}

Jawhari, Anass ^{[13
]}

Firpo, Matthew A. ^{[14
]}

Tuveson, David A. ^{[15
]}

Capunzo, Mario ^{[2
]}

Karin, Michael ^{[11
,12
]}

De Laurenzi, Vincenzo ^{[1
,9
]}

Turco, Maria Caterina ^{[1
,2
]}

机构：

[1] BIOUNIVERSA Srl, I-84084 Salerno, Italy

[2] Univ Salerno, Dept Med & Surg, I-84081 Salerno, Italy

[3] Univ Salerno, Div Biomed A Leone, Dept Pharm, I-84084 Salerno, Italy

[4] Ist Nazl Tumouri Fdn G Pascale, Pathol Unit, I-81100 Naples, Italy

[5] Ist Nazl Tumouri Fdn G Pascale, Anim Facil, I-81100 Naples, Italy

[6] Careggi Univ Hosp, Dept Oncol, Reconstruct Microsurg, I-50139 Florence, Italy

[7] CNRS, Inst Genet Mol Montpellier, UMR5535, F-34293 Montpellier, France

[8] Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol, NL-1105 AZ Amsterdam, Netherlands

[9] Univ G dAnnunzio, Dipartimento Sci Med Orali & Biotecnol, Ctr Studi Invecchiamento, CeSI MeT, I-66100 Chieti, Italy

[10] SS Annunziata Hosp, Div Surg Oncol, I-66100 Chieti, Italy

[11] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, San Diego, CA 92093 USA

[12] Univ Calif San Diego, Sch Med, Dept Pathol, Lab Gene Regulat & Signal Transduct, San Diego, CA 92093 USA

[13] CALIXAR, F-69008 Lyon, France

[14] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Surg, Salt Lake City, UT 84132 USA

[15] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

CANCER; PROTEIN; PROGRESSION; CELLS; INFLAMMATION; EXPRESSION; IL-17;

D O I：

10.1038/ncomms9695

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

引用

页数：11

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