Growth differentiation factor‐15 (GDF‐15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2)

Whitson, Ramon J.; Lucia, M. Scott; Lambert, James R.

doi:10.1002/jcb.24484

Cited by 34 publications

(25 citation statements)

References 77 publications

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“…GDF15 has been found to have pro- or anti-angiogenic effects based on the cellular microenvironment/stressor (Song et al, 2012; Whitson et al, 2013). HUVECs exposed to hyperoxia showed a robust induction in GDF15 mRNA and protein levels and this was higher in male cells.…”

Section: Discussionmentioning

confidence: 99%

Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro : Role of Hif-1α

Zhang

Jiang

Wang

et al. 2017

Toxicology and Applied Pharmacology

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Male premature neonates are more susceptible than females to the development of bronchopulmonary dysplasia (BPD). The reasons underlying sexually dimorphic outcomes in premature neonates are not known. GDF15 (Growth and differentiation factor 15) is a secreted cytokine and plays a role in cell proliferation, apoptosis, and angiogenesis. In this study, we sought to elucidate the sex-specific expression of Gdf15 in the lung in vivo in neonatal hyperoxic lung injury and its regulation by Hif-1α, and to delineate the differences in GDF15 expression in male and female human umbilical venous endothelial cells in an in vitro model of oxygen toxicity. Following hyperoxia exposure (95% FiO2, PND (postnatal day 1-5: saccular stage of lung development), neonatal male mice (C57BL/6) show increased GDF15 and decreased HIF-1α expression compared to female mice. For the in vitro experiments, male and female HUVECs were exposed to room air condition (21% O2, 5% CO2) or in hyperoxia condition (95% O2, 5% CO2) for up to 72 h. Male HUVECs had greater expression of GDF15 mRNA and protein. To study the inter-relationship between GDF15 and HIF-1α, we measured the expression of GDF15 in H441 cells after HIF-1α knockdown using promoter dual luciferase reporter assay, which showed that HIF-1α and GDF15 expression are inversely related under normoxia and hyperoxia. The results indicate that sex differences exist in the expression and modulation of GDF15 by HIF-1α in neonatal hyperoxic injury both in vivo and in vitro. These differences could explain in part the mechanisms behind sex-specific differences in BPD.

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Section: Discussionmentioning

confidence: 99%

Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro : Role of Hif-1α

Zhang

Jiang

Wang

et al. 2017

Toxicology and Applied Pharmacology

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“…Because p53 is a well known angiogenesis inhibitor (Teodoro et al, 2007), it is possible that MEG3 inhibits angiogenesis via activation of p53. Whitson et al (2013) recently demonstrated that GDF15, a MEG3 activated p53 target gene (Zhou et al, 2007), suppresses angiogenesis (Whitson et al, 2013). MEG3 plays an important role in suppression of human NFAs, likely through activation of p53.…”

Section: The P53 Connectionmentioning

confidence: 99%

Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma

Zhou

Zhang

Klibanski

2014

Molecular and Cellular Endocrinology

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Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes.

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“…In TRAMP (transgenic adenocarcinoma of the mouse prostate) mouse prostate cancer models, GDF-15 has been demonstrated to slow cancer development but increase metastases 49. Nevertheless, GDF-15 has been recently shown to suppress in-vitro angiogenesis through its interaction with connective tissue growth factor 13,50. It is involved in apoptotic pathways and is thought to play a role in antitumor activity of tasquinimod 13.…”

Section: Other Mechanisms Of Action Of Tasquinimodmentioning

confidence: 99%

Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer

Gupta¹,

Ustwani²,

Шен³

et al. 2014

OTT

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Castrate-resistant prostate cancer (CRPC) is a disease where survival is poor and treatment is challenging. Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC. However, despite the presence of new approved drugs such as enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and alpharadin, there is still an unmet need for novel agents with different mechanisms of action to target CRPC. Based on earlier studies demonstrating therapeutic potential of a quinoline-3-carboxamide agent roquinimex as an anticancer drug, efforts were directed to identify other useful members in this class. Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC. The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease. Tasquinimod is an orally available agent that has shown efficacy and favorable safety profile as deduced by the results of Phase I and II clinical trials of this drug in prostate cancer. The place of tasquinimod in the treatment of CRPC patients is currently under examination in an ongoing Phase III clinical trial. In this review, we will discuss tasquinimod, starting from its discovery and current knowledge on potential mechanisms of action to its clinical potential in CRPC.

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Growth differentiation factor‐15 (GDF‐15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2)

Cited by 34 publications

References 77 publications

Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro : Role of Hif-1α

Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro : Role of Hif-1α

Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma

Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer

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