Growth hormone in the tumor microenvironment

Chesnokova, Vera; Melmed, Shlomo

doi:10.20945/2359-3997000000186

Cited by 22 publications

(14 citation statements)

References 93 publications

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“…To add a little more complexity to the acromegaly and EMT relationship, it is worth to mention that one of the surprising effects of GH is the induction of EMT ( 83 ), closing the circle around EMT and acromegaly. The induction of EMT by GH seems to be mediated by the tumor microenvironment involving not only tumor cells but multiple non-tumoral cell types ( 84 , 85 ).…”

Section: Discussionmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly

et al. 2021

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Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors.

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Section: Discussionmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly

et al. 2021

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“…Repair of DNA damage and genome maintenance are crucially important in prevention of premature aging [ 2 3 ], and both GH and IGF-I are involved in these processes. Actions of both GH and IGF-I have been linked to development and progression of neoplastic disease [ 4 5 6 ]. Moreover, there is considerable epidemiological evidence for a positive association of height, a GH and IGF-I dependent trait, with various types of cancer in women and men [ 7 8 9 ].…”

Section: Growth Hormone Effects On Dna Damage and Repairmentioning

confidence: 99%

“…Moreover, there is considerable epidemiological evidence for a positive association of height, a GH and IGF-I dependent trait, with various types of cancer in women and men [ 7 8 9 ]. Cancerous cells can be affected not only by the pituitary derived (endocrine) GH, but also by the autocrine GH produced by tumors, including GH secreted by senescent cells within the tumor tissue [ 4 ]. Recent work provided new evidence for divergent actions of GH in cancer as compared to normal cells.…”

Section: Growth Hormone Effects On Dna Damage and Repairmentioning

confidence: 99%

Growth Hormone and Aging: New Findings

Bartke

Hascup

et al. 2021

World J Mens Health

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Complex relationships between growth hormone (GH) signaling and mammalian aging continue to attract attention of many investigators. Recent results include evidence that the impact of GH on genome maintenance (DNA damage and repair) is drastically different in normal as compared to cancer cells, consistent with GH promoting aging and cancer progression. Impact of GH on DNA methylation was studied as a possible mechanism linking actions of GH during early life to the trajectory of aging. Animals with reduced or enhanced GH signaling and novel animals with adipocyte-specific deletion of GH receptors were used to elucidate the effects of GH on white and brown adipose tissue, including the impact of this hormone on lipolysis, fibrosis, and thermogenesis. Effects of GH on adipose tissue related to lipid and energy metabolism emerge as mechanistic links between GH, healthspan, and lifespan. Treatment of healthy men with a combination of GH, dehydroepiandrosterone, and metformin was reported to restore thymus function and reduce epigenetic age. Studies of human subjects with deficiency of GH or GH receptors and studies of mice with the same endocrine syndromes identified several phenotypic changes related (positively or negatively) to the previously reported predisposition to healthy aging. Results of these and other recent studies advance present understanding of the mechanisms by which GH influences aging and longevity and of the trade-offs involved.

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“…Lobie and colleagues have reported that GH expression in tumors predicts a worse survival outcome in patients with mammary and endometrial carcinoma [41]. Melmed et al have demonstrated through a series of elegant studies that GH induces DNA damage and abrogates DNA damage repair (DDR) in normal colon tissues, alongside decreasing p53 expression by suppressing ATM kinases [42][43][44]. These actions of GH increase colon polyps and potentially direct oncogenesis and cancer progression in the colon; and indeed colon cancer incidence rates were found upregulated by several studies on acromegaly patients [22,45].…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Upregulates Mediators of Melanoma Drug Efflux and Epithelial-to-Mesenchymal Transition In Vitro and In Vivo

Qian

Basu

Mathes

et al. 2020

Cancers

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Growth hormone (GH) and the GH receptor (GHR) are expressed in a wide range of malignant tumors including melanoma. However, the effect of GH/insulin-like growth factor (IGF) on melanoma in vivo has not yet been elucidated. Here we assessed the physical and molecular effects of GH on mouse melanoma B16-F10 and human melanoma SK-MEL-30 cells in vitro. We then corroborated these observations with syngeneic B16-F10 tumors in two mouse lines with different levels of GH/IGF: bovine GH transgenic mice (bGH; high GH, high IGF-1) and GHR gene-disrupted or knockout mice (GHRKO; high GH, low IGF-1). In vitro, GH treatment enhanced mouse and human melanoma cell growth, drug retention and cell invasion. While the in vivo tumor size was unaffected in both bGH and GHRKO mouse lines, multiple drug-efflux pumps were up regulated. This intrinsic capacity of therapy resistance appears to be GH dependent. Additionally, epithelial-to-mesenchymal transition (EMT) gene transcription markers were significantly upregulated in vivo supporting our current and recent in vitro observations. These syngeneic mouse melanoma models of differential GH/IGF action can be valuable tools in screening for therapeutic options where lowering GH/IGF-1 action is important.

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Growth hormone in the tumor microenvironment

Cited by 22 publications

References 93 publications

Epithelial–Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly

Epithelial–Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly

Growth Hormone and Aging: New Findings

Growth Hormone Upregulates Mediators of Melanoma Drug Efflux and Epithelial-to-Mesenchymal Transition In Vitro and In Vivo

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