Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531
CheukMan C Au,
John B Furness,
Kara Britt,
Sofya Oshchepkova,
Heta Ladumor,
Kai Ying Soo,
Brid Callaghan,
Celine Gerard,
Giorgio Inghirami,
Vivek Mittal,
Yufeng Wang,
Xin Yun Huang,
Jason A Spector,
Eleni Andreopoulou,
Paul Zumbo,
Doron Betel,
Lukas Dow,
Kristy A Brown
Affiliations
CheukMan C Au
Department of Medicine, Weill Cornell Medicine, New York, United States; Centre for Cancer Research, Hudson Institute for Medical Research, Clayton, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, Australia
John B Furness
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia
Kara Britt
Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
Sofya Oshchepkova
Department of Medicine, Weill Cornell Medicine, New York, United States
Heta Ladumor
Department of Medicine, Weill Cornell Medicine, New York, United States; Weill Cornell Medicine - Qatar, Doha, Qatar
Kai Ying Soo
Centre for Cancer Research, Hudson Institute for Medical Research, Clayton, Australia
Brid Callaghan
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia
Celine Gerard
Centre for Cancer Research, Hudson Institute for Medical Research, Clayton, Australia
Giorgio Inghirami
Department of Pathology, Weill Cornell Medical College, New York, United States
Vivek Mittal
Department of Cardiothoracic Surgery, Department of Cell and Developmental Biology, Neuberger Berman Lung Cancer Center, Weill Cornell Medicine, New York, United States
Yufeng Wang
Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, United States
Xin Yun Huang
Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, United States
Jason A Spector
Department of Surgery, Weill Cornell Medicine, New York, United States
Eleni Andreopoulou
Department of Medicine, Weill Cornell Medicine, New York, United States
Paul Zumbo
Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, United States; Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States
Doron Betel
Department of Medicine, Weill Cornell Medicine, New York, United States; Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States
Lukas Dow
Department of Medicine, Weill Cornell Medicine, New York, United States
Department of Medicine, Weill Cornell Medicine, New York, United States; Centre for Cancer Research, Hudson Institute for Medical Research, Clayton, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, Australia
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 Gαi 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.
