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

Ashiya Buckels1, Yue Zhang1, Jing Jiang1

  • 1Department of Medicine Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA.

Biochemistry and Biophysics Reports
|January 1, 2020
PubMed

Insights

Melanoma cells highly express the growth hormone receptor (GHR). Targeting GHR with an antibody blocked melanoma cell invasion and migration, suggesting GHR as a potential therapeutic target for this aggressive skin cancer.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Melanoma is an aggressive skin cancer often driven by ERK pathway mutations.
  • Resistance to targeted therapies necessitates exploring alternative treatment strategies.
  • High growth hormone receptor (GHR) expression in melanoma cell lines was observed in the NCI-60 database.

Purpose of the Study:

  • To investigate the role of growth hormone receptor (GHR) signaling in melanoma.
  • To determine the effect of human growth hormone (GH) on melanoma cell behavior.
  • To evaluate the therapeutic potential of targeting GHR in melanoma.

Main Methods:

  • Analysis of NCI-60 database for GHR expression in melanoma cell lines.
  • Treatment of melanoma cell lines (WM35, SK-MEL 5, SK-MEL 28, SK-MEL 119) with human growth hormone (GH).
  • Assessment of GHR signaling, invasion, and migration following GH treatment.
  • Inhibition studies using a GHR monoclonal antibody (mAb) antagonist.
  • Detection of GH in conditioned medium (CM) from melanoma cell lines.
  • Analysis of basal phosphorylation of GHR, JAK2, and STAT5.

Main Results:

  • GH treatment activated GHR signaling in melanoma cell lines.
  • GH significantly increased melanoma cell invasion and migration.
  • A GHR mAb antagonist inhibited GH-induced invasion and migration.
  • Human melanoma cell lines produce GH, indicating autocrine/paracrine signaling.
  • Basal phosphorylation of GHR, JAK2, and STAT5 suggests constitutive signaling.

Conclusions:

  • Melanoma cells exhibit high expression of GHR and produce GH.
  • GH acts in an autocrine/paracrine manner to promote melanoma cell invasion and migration.
  • GHR represents a potential therapeutic target for melanoma treatment.
Keywords:
AutocrineGrowth hormone (GH)Growth hormone receptor (GHR)MelanomaParacrine

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