Potential Role of Human Growth Hormone in Melanoma Growth Promotion

Handler, Marc Z.; Ross, Andrew L.; Shiman, Michael I.; Elgart, George W.; Grichnik, James M.

doi:10.1001/archdermatol.2012.2149

Cited by 14 publications

(7 citation statements)

References 24 publications

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“…Additional information was unavailable, because no medical history had been reported for this patient, and the case was not reported as an SAE. Only limited case reports of melanoma in association with GH exposure are available in the literature, and these are reports from adults [32,33]. No cases of de novo leukaemia were observed in the GeNeSIS cohort of patients without previous malignancy.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Primary Cancer Incidence in Growth Hormone-Treated Children: Comparison of a Multinational Prospective Observational Study with Population Databases

et al. 2016

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Background/Aims: Although results of the majority of clinical studies have shown no association between growth hormone (GH) treatment in childhood and risk of primary cancer, concerns remain regarding the potential influence of GH therapy on neoplastic cell growth. This study evaluated the incidence of primary malignancies in a large observational study of paediatric GH treatment. Methods: Primary cancer incidence was assessed in a cohort of 19,054 GH-treated children without a reported prestudy history of malignancy in the observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). The standardised incidence ratio (SIR) for primary cancer in GH-treated children was determined by comparing cancer incidence in the GeNeSIS study population with incidence rates for country-, age-, and sex-matched cohorts of the general population. Results: During a mean follow-up of 3.4 years in GeNeSIS (64,705 person-years), 13 incident potential primary cancers were identified in GH-treated patients. The SIR (95% confidence interval) for all observed cancers was 1.02 (0.54-1.75), and the crude incidence was 20.1 (10.7-34.4) cases per 100,000 person-years. Conclusion: Acknowledging the relatively short follow-up in our study, GH-treated children without a history of previous malignancy did not have a higher risk of all-site primary cancer during the study when compared to general-population cancer registries.

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Section: Discussionmentioning

confidence: 99%

Assessment of Primary Cancer Incidence in Growth Hormone-Treated Children: Comparison of a Multinational Prospective Observational Study with Population Databases

et al. 2016

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“…In the first, a 26 year old was diagnosed with malignant melanoma following multiple hormone replacement therapy that included GH [36]. In the second, a husband and wife were both diagnosed with melanoma within two weeks of each other following three months of daily GH injections taken as part of an “anti-aging regimen” [37]. Although a cause and effect issue cannot be distilled here, the short length of time between the start of GH exposure and diagnosis of melanoma in these patients is remarkable.…”

Section: Discussionmentioning

confidence: 99%

Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

Sustarsic

Junnila

Kopchick

2013

Biochemical and Biophysical Research Communications

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Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma.

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“…also occur along with driving mutations in precursor cells, setting the stage for melanoma development upon activation. The activating signal is unknown but could be inflammatory-/ cytokine-induced (42)(43)(44)(45)(46)(47)(48)(49). Once activated, cells would attempt to follow normal developmental/regenerative pathways towards the epidermis; however, the presence of the aforementioned mutation and its interaction with other genetic and environmental factors would cause cellular proliferation/migration in different patterns (32).…”

Section: Dermal Precursor Modelmentioning

confidence: 99%

“…Pathways driving or suppressing activation of the cells could also be studied. These pathways may include inflammatory pathways or cytokines associated with eruptive nevi (44,45,49). Pathway suppression may prevent mole and melanoma development.…”

Section: To What Extent Can Initiated Cells Remain Dormant and What Amentioning

confidence: 99%

How, and from which cell sources, do nevi really develop?

Grichnik

Ross

Schneider

et al. 2014

Experimental Dermatology

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Melanocytic neoplasms are a diverse group of benign and malignant tumors with variable clinical features. While some models still promote the epidermal melanocyte as the origin of melanocytic neoplasms, clinical findings are inconsistent with this theory for the majority of tumors. Despite advances in naevus and melanoma biology, the location and differentiation status of the cell of origin remains undefined. Germ line genetics, biological state and cellular location of the mutated cell, as well as local environmental factors all likely play a role in the development of melanocytic neoplasms. Herein, we will review potential models for melanocytic neoplasia and discuss research challenges and opportunities.

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Potential Role of Human Growth Hormone in Melanoma Growth Promotion

Cited by 14 publications

References 24 publications

Assessment of Primary Cancer Incidence in Growth Hormone-Treated Children: Comparison of a Multinational Prospective Observational Study with Population Databases

Assessment of Primary Cancer Incidence in Growth Hormone-Treated Children: Comparison of a Multinational Prospective Observational Study with Population Databases

Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

How, and from which cell sources, do nevi really develop?

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