Endothelin B Receptor Blockade Inhibits Dynamics of Cell Interactions and Communications in Melanoma Cell Progression

Bagnato, Anna; Rosanò, Laura; Spinella, Francesca; Castro, Valeriana Di; Tecce, Raffaele; Natali, Pier Giorgio

doi:10.1158/0008-5472.can-03-2344

Cited by 122 publications

(141 citation statements)

References 33 publications

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“…In ovarian cancer, endothelin-1 (ET-1) plays a key role in the development and progression of this tumor, promoting tumor cell proliferation (14,15), apoptosis protection (16), invasiveness (17), and neovascularization (18 -21). ET-1 and its selective receptor ET A (ET A R) are overexpressed in primary and metastatic ovarian carcinoma as compared with normal ovarian tissue (22).…”

Section: Cyclooxygenase (Cox)mentioning

confidence: 99%

“…ET-1 and its selective receptor ET A (ET A R) are overexpressed in primary and metastatic ovarian carcinoma as compared with normal ovarian tissue (22). ET-1/ET A R interaction results in activation of a pertussis toxin-insensitive G protein that stimulates phospholipase C activity and increases intracellular Ca 2ϩ levels as well as activation of protein kinase C, mitogen-activated protein kinase (MAPK), paxillin, and p125 focal adhesion kinase (23).…”

Section: Cyclooxygenase (Cox)mentioning

confidence: 99%

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Endothelin-1-induced Prostaglandin E2-EP2, EP4 Signaling Regulates Vascular Endothelial Growth Factor Production and Ovarian Carcinoma Cell Invasion

Spinella¹,

Rosanò²,

Castro³

et al. 2004

Journal of Biological Chemistry

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Cyclooxygenase (COX)-1-and COX-2-derived prostaglandins are implicated in the development and progression of several malignancies. We have recently demonstrated that treatment of ovarian carcinoma cells with endothelin-1 (ET-1) induces expression of both COX-1 and COX-2, which contributes to vascular endothelial growth factor (VEGF) production. In this study, we show that in HEY and OVCA 433 ovarian carcinoma cells, ET-1, through the binding with ET A receptor (ET A R), induces prostaglandin E2 (PGE 2 ) production, as the more represented PG types, and increases the expression of PGE 2 receptor type 2 (EP2) and type 4 (EP4). The use of pharmacological EP agonists and antagonists indicates that ET-1 and PGE 2 stimulate VEGF production principally through EP2 and EP4 receptors. At the mechanistic level, we prove that the induction of PGE 2 and VEGF by ET-1 involves Src-mediated epidermal growth factor receptor transactivation. Finally, we demonstrate that ET A R-mediated activation of PGE 2 -dependent signaling participates in the regulation of the invasive behavior of ovarian carcinoma cells by activating tumor-associated matrix metalloproteinase. These results implicate EP2 and EP4 receptors in the induction of VEGF expression and cell invasiveness by ET-1 and provide a mechanism by which ET A R/ET-1 can promote and interact with PGE 2 -dependent machinery to amplify its proangiogenic and invasive phenotype in ovarian carcinoma cells. Pharmacological blockade of ET A R can therefore represent an additional strategy to control PGE 2 signaling, which has been associated with ovarian carcinoma progression.

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Section: Cyclooxygenase (Cox)mentioning

confidence: 99%

Section: Cyclooxygenase (Cox)mentioning

confidence: 99%

Endothelin-1-induced Prostaglandin E2-EP2, EP4 Signaling Regulates Vascular Endothelial Growth Factor Production and Ovarian Carcinoma Cell Invasion

Spinella¹,

Rosanò²,

Castro³

et al. 2004

Journal of Biological Chemistry

Self Cite

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“…The endothelin system may contribute to tumor growth and progression by multiple mechanisms, including cell proliferation, angiogenesis, and escape from apoptosis [17]. Bosentan, a non-peptide orally active dual ET A and ET B receptor antagonist, inhibited melanoma cell proliferation in vitro in all examined cell lines and in a mouse xenograft model [18].…”

Section: Introductionmentioning

confidence: 99%

A Phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma

Kefford

Beith

Hazel³

et al. 2006

Invest New Drugs

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SummaryThere is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity.This multicenter, open-label, single-arm, prospective, proof-of-concept study assessed the effects of bosentan monotherapy (500 mg oral tablets, bid) on tumor response in patients with stage IV metastatic melanoma. Patients were treated until disease progression, death or serious adverse event leading to premature study drug discontinuation. Tumor response was assessed at 6-weekly intervals R. Kefford ( ) · R. Kusic

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“…ET-1 has been studied most extensively and has been shown to modulate endothelial cell proliferation, migration, invasion, and microtubule formation. More interestingly, ET-1 increases VEGF mRNA expression and VEGF protein levels, indicating probable cross-talk between the endothelin-axis and VEGF signaling (54). Compared with normal urothelium, increased expression of ET-1 and the associated endothelin-A-and endothelin-B-receptors has been found in the vast majority of invasive bladder cancer specimens (55).…”

Section: Angiogenesis and Its Inhibitorsmentioning

confidence: 99%

Novel targeted agents for the treatment of bladder cancer: translating laboratory advances into clinical application

Yang

Flaig

2010

Int. braz j urol.

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Bladder cancer is a common and frequently lethal cancer. Natural history studies indicate two distinct clinical and molecular entities corresponding to invasive and non-muscle invasive disease. The high frequency of recurrence of noninvasive bladder cancer and poor survival rate of invasive bladder cancer emphasizes the need for novel therapeutic approaches. These mechanisms of tumor development and promotion in bladder cancer are strongly associated with several growth factor pathways including the fibroblast, epidermal, and the vascular endothelial growth factor pathways. In this review, efforts to translate the growing body of basic science research of novel treatments into clinical applications will be explored.

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Endothelin B Receptor Blockade Inhibits Dynamics of Cell Interactions and Communications in Melanoma Cell Progression

Abstract: ABSTRACT

Cited by 122 publications

References 33 publications

Endothelin-1-induced Prostaglandin E2-EP2, EP4 Signaling Regulates Vascular Endothelial Growth Factor Production and Ovarian Carcinoma Cell Invasion

Endothelin-1-induced Prostaglandin E2-EP2, EP4 Signaling Regulates Vascular Endothelial Growth Factor Production and Ovarian Carcinoma Cell Invasion

A Phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma

Novel targeted agents for the treatment of bladder cancer: translating laboratory advances into clinical application

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