Autocrine/paracrine actions of growth hormone in human melanoma cell lines

Ashiya Buckels; Yue Zhang; Jing Jiang; Mohammad Athar; Farrukh Afaq; Lalita Shevde-Samant; Stuart J. Frank

Biochemistry and Biophysics Reports (Mar 2020)

Autocrine/paracrine actions of growth hormone in human melanoma cell lines

Ashiya Buckels,
Yue Zhang,
Jing Jiang,
Mohammad Athar,
Farrukh Afaq,
Lalita Shevde-Samant,
Stuart J. Frank

Affiliations

Ashiya Buckels: Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
Yue Zhang: Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
Jing Jiang: Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
Mohammad Athar: Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
Farrukh Afaq: Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
Lalita Shevde-Samant: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
Stuart J. Frank: Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA; Medical Service, Veterans Affairs Medical Center, Birmingham, AL, USA; Corresponding author. Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA.

Journal volume & issue: Vol. 21

Abstract

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Melanoma is the most aggressive skin cancer. Its aggressiveness is most commonly attributed to ERK pathway mutations leading to constitutive signaling. Though initial tumor regression results from targeting this pathway, resistance often emerges. Interestingly, interrogation of the NCI-60 database indicates high growth hormone receptor (GHR) expression in melanoma cell lines. To further characterize melanoma, we tested responsiveness to human growth hormone (GH). GH treatment resulted in GHR signaling and increased invasion and migration, which was inhibited by a GHR monoclonal antibody (mAb) antagonist in WM35, SK-MEL 5, SK-MEL 28 and SK-MEL 119 cell lines. We also detected GH in the conditioned medium (CM) of human melanoma cell lines. GHR, JAK2 and STAT5 were basally phosphorylated in these cell lines, consistent with autocrine/paracrine GH production. Together, our results suggest that melanomas are enriched in GHR and produce GH that acts in an autocrine/paracrine manner. We suggest that GHR may constitute a therapeutic target in melanoma. : Implications: The GHR signaling pathway may prove a useful therapeutic target in melanoma cells. Keywords: Melanoma, Growth hormone (GH), Growth hormone receptor (GHR), Autocrine, Paracrine

Published in Biochemistry and Biophysics Reports

ISSN: 2405-5808 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: http://www.journals.elsevier.com/biochemistry-and-biophysics-reports/

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