Abstract 5208
Background
Growth hormone (GH) signalling is initiated by binding of GH to the GH receptor (GHR) and activation of Janus kinase 2, which in turn, promotes phosphorylation of STAT5, PI3K/AKT and MAPK. High levels of GHR expression have been reported in melanoma. This project aims to characterise GH signalling in primary melanoma cell lines and identify cell lines which respond to GH and GHR inhibition, with a view to testing in preclinical xenograft studies.
Methods
Over 24 cell lines established at the Auckland Cancer Society Research Centre (ACSRC) in New Zealand were tested for response to GH, prolactin (PRL) and a GHR antagonist, by assessing STAT5 phosphorylation by western blot. mRNA expression was assessed by Nanostring PlexSet. Endogenous protein was assessed by ELISA.
Results
From the panel of melanoma cell lines, 62% responded to GH stimulation and GHR inhibition. mRNA expression analysis demonstrated that the IGF1 receptor and GHR were highly expressed across cell lines. Most of the cell lines expressing GHR mRNA responded to GH. GH1 mRNA was expressed at very low levels in a subset of cell lines, and ELISA analysis confirmed the presence of endogenous GH protein. siRNA-mediated knockdown of the GHR reduced GHR mRNA expression and STAT5 phosphorylation by GH. GH increased cell viability in a subset of melanoma cell lines. A vemurafenib-resistant melanoma cell line and B16/F10 mouse cell line were also sensitive to GH and GHR inhibition. Exon analysis will be performed for GH and related genes.
Conclusions
In this study, we have demonstrated GH stimulates signal transduction and promotes enhance of viability of primary melanoma cell lines, and that GHR blockade prevents this effect, indicating that blocking GHR signalling might be a useful strategy to treat melanoma. The next step is to understand whether GHR inhibition plays a role in regulating tumour growth in vivo.
Clinical trial identification
Editorial acknowledgement
Li Family PhD Scholarship.
Legal entity responsible for the study
Peter Shepherd.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
920 - Efficacy of intravenous (IV) NEPA, a fixed NK1/5-HT3 receptor antagonist (RA) combination, for prevention of CINV following cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy (CT)
Presenter: Lee Schwartzberg
Session: Poster Display session 1
Resources:
Abstract
5146 - Efficacy of olanzapine combination in prevention of nausea & vomiting in highly emetogenic chemotherapy
Presenter: Smitha Saldanha
Session: Poster Display session 1
Resources:
Abstract
1947 - Patient-reported outcome data during real-world use of NEPA for prevention of chemotherapy-induced nausea and vomiting in high-risk platin-receiving patients - A prospective multicenter trial
Presenter: Meinolf Karthaus
Session: Poster Display session 1
Resources:
Abstract
6163 - A study evaluating steroid induced metabolic syndrome after antiemetic dexamethasone therapy in patients received high emetic risk chemotherapy
Presenter: Hee Jun Kim
Session: Poster Display session 1
Resources:
Abstract
2154 - High incidence of nausea during initial and repeated courses if intravenous chemotherapy in patients receiving guideline consistent antiemetic prophylaxis - a prospective, observational, real world study.
Presenter: Teresa Smit
Session: Poster Display session 1
Resources:
Abstract
1637 - "Randomised controlled trial of Scalp Cooling (SC) for the prevention of Chemotherapy Induced Alopecia (CIA)”
Presenter: Jyoti Bajpai
Session: Poster Display session 1
Resources:
Abstract
5351 - Performance of the ‘4S rule’ to predict short-term outcomes in cancer outpatients with unsuspected pulmonary embolism.
Presenter: David Pesántez Coronel
Session: Poster Display session 1
Resources:
Abstract
1189 - Prevalence of venous thromboembolism based on intensive screening for patients with advanced solid tumor in prospective observational study
Presenter: Shota Omori
Session: Poster Display session 1
Resources:
Abstract
4340 - Short-term outcomes of cancer patients with pulmonary embolism according to the setting (hospital-acquired vs. outpatient) at diagnosis.
Presenter: Diego Muñoz Guglielmetti
Session: Poster Display session 1
Resources:
Abstract
4658 - Patient-reported outcomes associated with switching to rivaroxaban for the treatment of venous thromboembolism (VTE) in patients with active cancer
Presenter: Alexander Cohen
Session: Poster Display session 1
Resources:
Abstract