β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

被引：315

作者：

Renz, Bernhard W. ^{[1
,2
,3
]}

Takahashi, Ryota ^{[2
,3
]}

Tanaka, Takayuki ^{[2
,3
]}

Macchini, Marina ^{[2
,3
,4
]}

Hayakawa, Yoku ^{[2
,3
,5
]}

Dantes, Zahra ^{[6
]}

Maurer, H. Carlo ^{[2
,3
]}

Chen, Xiaowei ^{[2
,3
]}

Jiang, Zhengyu ^{[2
,3
]}

Westphalen, C. Benedikt ^{[2
,3
,7
]}

Ilmer, Matthias ^{[1
]}

Valenti, Giovanni ^{[2
,3
]}

Mohanta, Sarajo K. ^{[8
]}

Habenicht, Andreas J. R. ^{[8
]}

Middelhoff, Moritz ^{[2
,3
]}

Chu, Timothy ^{[2
,3
]}

Nagar, Karan ^{[2
,3
]}

Tailor, Yagnesh ^{[2
,3
]}

Casadei, Riccardo ^{[9
]}

Di Marco, Mariacristina ^{[10
]}

Kleespies, Axel ^{[1
]}

Friedman, Richard A. ^{[11
]}

Remotti, Helen ^{[12
]}

Reichert, Maximilian ^{[6
]}

Worthley, Daniel L. ^{[2
,3
,13
]}

Neumann, Jens ^{[14
]}

Werner, Jens ^{[1
]}

Iuga, Alina C. ^{[12
]}

Olive, Kenneth P. ^{[2
,3
,12
]}

Wang, Timothy C. ^{[2
,3
]}

机构：

[1] Hosp Univ Munich, Dept Gen Visceral & Transplantat Surg, D-81377 Munich, Germany

[2] Columbia Univ, Med Ctr, Dept Digest & Liver Dis, 1130 St Nicholas Ave, New York, NY 10032 USA

[3] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, 1130 St Nicholas Ave, New York, NY 10032 USA

[4] IRCCS, San Raffaele Sci Inst, Dept Oncol, I-20132 Milan, Italy

[5] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Tokyo 1138655, Japan

[6] Tech Univ Munich, Klinikum Rechts Isar, Dept Med 2, D-81675 Munich, Germany

[7] Hosp Univ Munich, Dept Internal Med 3, D-81377 Munich, Germany

[8] Univ Munich, Inst Cardiovasc Prevent, D-80336 Munich, Germany

[9] Univ Bologna, Alma Mater Studiorum, Dept Internal Med & Surg DIMEC, St Orsola Malpighi Hosp, I-40138 Bologna, Italy

[10] Univ Bologna, St Orsola Malpighi Hosp, Dept Expt Diagnost & Specialty Med, I-40138 Bologna, Italy

[11] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Biomed Informat Shared Resource, Dept Biomed Informat,Med Ctr, New York, NY 10032 USA

[12] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA

[13] Univ Adelaide, Dept Med, Adelaide, SA 5005, Australia

[14] Hosp Univ Munich, Dept Pathol, D-81377 Munich, Germany

来源：

CANCER CELL | 2018年 / 33卷 / 01期

关键词：

DUCTAL ADENOCARCINOMA; TUMOR-GROWTH; PERINEURAL INVASION; NEURAL INVASION; CELLS; EXPRESSION; SURVIVAL; BLOCKERS; NEURONS; NERVE;

D O I：

10.1016/j.ccell.2017.11.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras(+/G12D);Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras(+/G12D); LSL-Trp53(+/R172H);Pdx1-Cre (KPC) mice. Therapy with a Trk inhibitor together with gemcitabine also increased survival of KPC mice. Analysis of PDAC patient cohorts revealed a correlation between brain-derived neurotrophic factor (BDNF) expression, nerve density, and increased survival of patients on nonselective beta-blockers. These findings suggest that catecholamines drive a feedforward loop, whereby upregulation of neurotrophins increases sympathetic innervation and local norepinephrine accumulation.

引用

页码：75 / +

页数：23

共 50 条

[1] AN ADRENERGIC-NEUROTROPHIN FEEDFORWARD LOOP PROMOTES PANCREATIC CANCER
不详
CANCER DISCOVERY, 2018, 8 (02) : 138 - 138
[2] β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer (vol 33, pg 75, 2018)
Renz, Bernhard W.
Takahashi, Ryota
Tanaka, Takayuki
Macchini, Marina
Hayakawa, Yoku
Dantes, Zahra
Maurer, H. Carlo
Chen, Xiaowei
Jiang, Zhengyu
Westphalen, C. Benedikt
Ilmer, Matthias
Valenti, Giovanni
Mohanta, Sarajo K.
Habenicht, Andreas J. R.
Middelhoff, Moritz
Chu, Timothy
Nagar, Karan
Tailor, Yagnesh
Casadei, Riccardo
Di Marco, Mariacristina
Kleespies, Axel
Friedman, Richard A.
Remotti, Helen
Reichert, Maximilian
Worthley, Daniel L.
Neumann, Jens
Werner, Jens
Iuga, Alina C.
Olive, Kenneth P.
Wang, Timothy C.
CANCER CELL, 2018, 34 (05) : 863 - 867
[3] Pancreatic cancer progression via β2 adrenergic-neurotrophin feed forward loop
Takahashi, Ryota
Ijichi, Hideaki
Koike, Kazuhiko
CANCER SCIENCE, 2022, 113
[4] A novel β 2 adrenergic-nerve growth factor feed forward loop promotes pancreatic cancer
Renz, Bernhard W.
Macchini, Marina
Hayakawa, Yoku
Chen, Xiaowei
Jiang, Zhengyu
Tanaka, Takayuki
Westphalen, C. Benedikt
Tailor, Yagnesh
Werner, Jens
Kleespies, Axel
Iuga, Alina C.
Worthley, Daniel L.
Olive, Kenneth P.
Wang, Timothy C.
CANCER RESEARCH, 2016, 76
[5] Neuro-Mesenchymal Interaction Mediated by a β2-Adrenergic Nerve Growth Factor Feedforward Loop Promotes Colorectal Cancer Progression
Kobayashi, Hiroki
Iida, Tadashi
Ochiai, Yosuke
Malagola, Ermanno
Zhi, Xiaofei
White, Ruth A.
Qian, Jin
Wu, Feijing
Waterbury, Quin T.
Tu, Ruhong
Zheng, Biyun
Labella, Jonathan S.
Zamechek, Leah B.
Ogura, Atsushi
Woods, Susan L.
Worthley, Daniel L.
Enomoto, Atsushi
Wang, Timothy C.
CANCER DISCOVERY, 2025, 15 (01) : 202 - 226
[6] Adrenergic Signaling Promotes Pancreatic Cancer Initiation and Progression
Renz, Bernhard W.
Westphalen, Christoph B.
Chen, Xiaowei
Hayakawa, Yoku
Worthley, Daniel L.
Macchini, Marina
Asfaha, Samuel
Kleespies, Axel
Remotti, Helen
Olive, Kenneth P.
Wang, Timothy C.
GASTROENTEROLOGY, 2014, 146 (05) : S487 - S487
[7] NUSAP1-LDHA-Glycolysis-Lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma
Chen, Ming
Cen, Kaili
Song, Yinjing
Zhang, Xiaochen
Liou, Yih-Cherng
Liu, Pu
Huang, Jinyan
Ruan, Jian
He, Jia
Ye, Wanyi
Wang, Tianyue
Huang, Xing
Yang, Jiaqi
Jia, Yunlu
Liang, Xue
Shen, Peng
Wang, Qingqing
Liang, Tingbo
CANCER LETTERS, 2023, 567
[8] Positive Feedback Loop of Pancreatic Endocrine-Exocrine Signaling Promotes the Occurrence and Development of Pancreatic Cancer
不详
PANCREAS, 2022, 51 (07) : 844 - 844
[9] Myeloid adrenergic signaling via CaMKII forms a feedforward loop of catecholamine biosynthesis
Luo, Yan
Liu, Bilian
Yang, Xin
Ma, Xiaoxiao
Zhang, Xing
Bragin, Denis E.
Yang, Xuexian O.
Huang, Wendong
Liu, Meilian
JOURNAL OF MOLECULAR CELL BIOLOGY, 2017, 9 (05) : 422 - 434
[10] Adrenergic signaling promotes pancreatic tumor initiation and progression
Renz, Bernhard W.
Westphalen, Christoph B.
Chen, Xiaowei
Hayakawa, Yoku
Takemoto, Yoshihiro
Macchini, Marina
Worthley, Daniel L.
Asfaha, Samuel
Kleespies, Axel
Remotti, Helen
Olive, Kenneth P.
Wang, Timothy C.
CANCER RESEARCH, 2015, 75

← 1 2 3 4 5 →