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

doi:10.7554/eLife.56913

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

Research output: Contribution to journal › Article

Abstract

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.

Original language	English (US)
Article number	e56913
Pages (from-to)	1-27
Number of pages	27
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.56913
State	Published - Jul 2020

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

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Au, C. C., Furness, J. B., Britt, K., Oshchepkova, S., Ladumor, H., Soo, K. Y., Callaghan, B., Gerard, C., Inghirami, G., Mittal, V., Wang, Y., Huang, X. Y., Spector, J. A., Andreopoulou, E., Zumbo, P., Betel, D., Dow, L., & Brown, K. A. (2020). Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and azp-531. eLife, 9, 1-27. [e56913]. https://doi.org/10.7554/eLife.56913

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and azp-531. / Au, Cheukman C.; Furness, John B.; Britt, Kara; Oshchepkova, Sofya; Ladumor, Heta; Soo, Kai Ying; Callaghan, Brid; Gerard, Celine; Inghirami, Giorgio; Mittal, Vivek; Wang, Yufeng; Huang, Xin Yun; Spector, Jason A.; Andreopoulou, Eleni; Zumbo, Paul; Betel, Doron; Dow, Lukas; Brown, Kristy A.

In: eLife, Vol. 9, e56913, 07.2020, p. 1-27.

Research output: Contribution to journal › Article

Au, CC, Furness, JB, Britt, K, Oshchepkova, S, Ladumor, H, Soo, KY, Callaghan, B, Gerard, C, Inghirami, G, Mittal, V, Wang, Y, Huang, XY, Spector, JA, Andreopoulou, E, Zumbo, P, Betel, D, Dow, L & Brown, KA 2020, 'Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and azp-531', eLife, vol. 9, e56913, pp. 1-27. https://doi.org/10.7554/eLife.56913

Au, Cheukman C. ; Furness, John B. ; Britt, Kara ; Oshchepkova, Sofya ; Ladumor, Heta ; Soo, Kai Ying ; Callaghan, Brid ; Gerard, Celine ; Inghirami, Giorgio ; Mittal, Vivek ; Wang, Yufeng ; Huang, Xin Yun ; Spector, Jason A. ; Andreopoulou, Eleni ; Zumbo, Paul ; Betel, Doron ; Dow, Lukas ; Brown, Kristy A. / Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and azp-531. In: eLife. 2020 ; Vol. 9. pp. 1-27.

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abstract = "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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AU - Spector, Jason A.

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