Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells

Pífano, Marina; Garona, Juan; Capobianco, Carla S.; González, Nazareno; Alonso, Daniel F.; Ripoll, Giselle Vanina

doi:10.3389/fonc.2017.00011

Cited by 27 publications

(38 citation statements)

References 48 publications

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“…However, ectopic expression of AVP and its receptors has been reported in breast, pancreatic, colorectal and gastrointestinal cancers, and small cell lung carcinoma [4,5]. While V1R activation has been observed to increase tumor cell growth [6,7], V2R agonists are generally known to have angiostatic, anti-proliferative and/or anti-metastatic effects in breast, lung and colorectal cancers [8][9][10]. However, in contrast to these protective roles of V2R, one study reported that V2R activation increased cell proliferation of ccRCC cell lines of human origin in vitro [11].…”

Section: Introductionmentioning

confidence: 99%

Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy

et al. 2019

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Arginine vasopressin (AVP) and its type-2 receptor (V2R) play an essential role in the regulation of salt and water homeostasis by the kidneys. V2R activation also stimulates proliferation of renal cell carcinoma (RCC) cell lines in vitro. The current studies investigated V2R expression and activity in human RCC tumors, and its role in RCC tumor growth. Examination of the cancer genome atlas (TCGA) database, and analysis of human RCC tumor tissue microarrays, cDNA arrays and tumor biopsy samples demonstrated V2R expression and activity in clear cell RCC (ccRCC). In vitro, V2R antagonists OPC31260 and Tolvaptan, or V2R gene silencing reduced wound closure and cell viability of 786-O and Caki-1 human ccRCC cell lines. Similarly in mouse xenograft models, Tolvaptan and OPC31260 decreased RCC tumor growth by reducing cell proliferation and angiogenesis, while increasing apoptosis. In contrast, the V2R agonist dDAVP significantly increased tumor growth. High intracellular cAMP levels and ERK1/2 activation were observed in human ccRCC tumors. In mouse tumors and Caki-1 cells, V2R agonists reduced Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Section: Introductionmentioning

confidence: 99%

Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy

et al. 2019

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“…Another reason for caution is that experiments on select tumour cell lines have suggested an inhibitory effect of the hormone. Recently for example, Pifano et al [ 33 ] reported on an anti-proliferative effect mediated by the V2-receptor in a tumour cell xenograft model. Such observations would argue against the use of a V2-receptor antagonist in cancer patients; yet there is no evidence in the literature that treatment with an antagonist promotes growth or spread of cancer.…”

Section: Discussionmentioning

confidence: 99%

Hyponatremia and V2 vasopressin receptor upregulation: a result of HSP90 inhibition

Yang

Puhm

Freissmuth

et al. 2017

Cancer Chemother Pharmacol

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Purpose Small-molecule inhibitors of heat-shock protein 90 (HSP90) have been under development as chemotherapeutic agents. The adverse events reported from early clinical trials included hyponatremia. Given the limited number of patients enrolled, the number of hyponatremia incidents was remarkable and repeatedly, the event was judged as severe. Inappropriate V2 vasopressin receptor stimulation is an established cause of hyponatremia. We explored the hypothesis that HSP90 inhibition produces hypersensitivity to vasopressin by upregulating V2-receptors.MethodsExperiments were carried out in cell culture using HEK293 cells with heterologous expression of the human V2-receptor and HELA cells with an endogenous V2-receptor complement. We tested the effect of HSP90 inhibition by three structurally unrelated compounds (alvespimycin, luminespib, radicicol) and asserted its specificity in cells depleted of cytosolic HSP90 (by RNA interference). Assays encompassed surface V2-receptor density and vasopressin-stimulated formation of cyclic AMP (cAMP).ResultsThe results demonstrate a twofold increase in cell-surface receptor density following pre-incubation with each of the HSP90 inhibitors. The effect had a concentration-dependence consistent with the individual potencies to inhibit HSP90. Similarly, depletion of cytosolic HSP90 increased surface-receptor density and at the same time, reduced the inhibitor effect. Upregulated V2-receptors were fully functional; hence, in culture treated with an HSP90 inhibitor, addition of vasopressin resulted in higher levels of cAMP than in controls.ConclusionSince formation of cAMP is the first signalling step in raising water permeability of the collecting duct epithelia, we suggest that V2-receptor upregulation generates hypersensitivity to vasopressin linking HSP90 inhibition to the development of hyponatremia.

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“…Our team has reported that the vasopressin analog desmopressin, a selective agonist for the vasopressin receptor 2 (AVPR2), significantly reduced tumor cell growth and migration in AR-negative CRPC (3). In vitro exposure to desmopressin also induced a dramatic decrease of the neuroendocrine markers chromogranin and neuron-specific enolase in aggressive CRPC cells (3). In prostate cancer, neuroendocrine transdifferentiation is known to be related with transition toward AR-indifference and metastatic phenotype.…”

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confidence: 95%