Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531

被引：8
作者：
Au, CheukMan C. [1 ,2 ,3 ]
Furness, John B. [4 ]
Britt, Kara [5 ,6 ]
Oshchepkova, Sofya [1 ]
Ladumor, Heta [1 ,7 ]
Soo, Kai Ying [2 ]
Callaghan, Brid [4 ]
Gerard, Celine [2 ]
Inghirami, Giorgio [8 ]
Mittal, Vivek [9 ]
Wang, Yufeng [10 ]
Huang, Xin Yun [10 ]
Spector, Jason A. [11 ]
Andreopoulou, Eleni [1 ]
Zumbo, Paul [10 ,12 ]
Betel, Doron [1 ,13 ]
Dow, Lukas [1 ]
Brown, Kristy A. [1 ,2 ,3 ]
机构：
[1] Weill Cornell Med, Dept Med, New York, NY 10065 USA
[2] Hudson Inst Med Res, Ctr Canc Res, Clayton, Vic, Australia
[3] Monash Univ, Dept Mol & Translat Sci, Clayton, Vic, Australia
[4] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic, Australia
[5] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
[6] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
[7] Weill Cornell Med Qatar, Doha, Qatar
[8] Weill Cornell Med Coll, Dept Pathol, New York, NY USA
[9] Weill Cornell Med, Dept Cardiothorac Surg, Dept Cell & Dev Biol, Neuberger Berman Lung Canc Ctr, New York, NY USA
[10] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA
[11] Weill Cornell Med, Dept Surg, New York, NY USA
[12] Weill Cornell Med Coll, Appl Bioinformat Core, New York, NY USA
[13] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA
来源：
ELIFE | 2020年 / 9卷
基金：
英国医学研究理事会;
关键词：
DES-ACYL GHRELIN; CYCLIC-AMP; PROLIFERATION; EXPRESSION; PATHWAY; CAMP; STIMULATION; MUTATIONS; RECEPTORS; ESTROGEN;
D O I：
10.7554/eLife.56913
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, remains the second leading cause of cancer-related death. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP-531. We report potent anti-tumor effects of unacylated ghrelin, dependent on cells being cultured in 3D in a biologically-relevant extracellular matrix. The mechanism of unacylated ghrelin-mediated growth inhibition involves activation of Gai and suppression of MAPK signaling. AZP-531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.
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页码：1 / 27
页数：27
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