Modulation of growth and urokinase secretion by vasopressin and closely related nonapeptides in metastatic mouse mammary tumor cells

Alonso, Daniel F.; Skilton, G; Fariña, Hernán G.; Lorenzo, Mariana S. De; Gómez, Daniel E.

doi:10.3892/ijo.10.2.375

Cited by 4 publications

(3 citation statements)

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“…The in vitro results of the present study are in agreement with those of other studies that have shown that the addition of DDAVP to mouse and human mammary cancer cells inhibits cell proliferation (38, 39). The antiproliferative action of DDAVP appears to be mediated trough the V 2 vasopressin receptor, which involves the increase of intracellular cAMP concentrations (22).…”

Section: Discussionsupporting

confidence: 93%

Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

et al. 2016

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Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% of them are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient’s overall survival. The aim of the present study was to evaluate the effects of two peptides on proliferation of a canine mammary cancer cell line derived from a simple carcinoma. The cell line CMT-U27 was grown in 96-well plates, at two cell densities (4 × 103 and 8 × 103 cells/well). Cultures were treated with oxytocin (OT) or desmopressin at five concentrations (10, 50, 100, 500, and 1000 nM). After 72 h of incubation, cell proliferation was determined by the MTT assay. Results showed that with 4 × 103 cells/well, OT at 50, 500, and 1000 nM was growth inhibitory for the cells, being statistically significant at 1000 nM. On the contrary, no antiproliferative effect was observed with 10 or 100 nM. At 8 × 103 cells/well, OT showed a significant antiproliferative effect only with the highest concentration (1000 nM). Desmopressin at 4 × 103 cells/well decreased cell viability at concentrations of 50, 100, 500, and 1000 nM (statistically significant with the highest concentration), while no effect was observed with 10 nM. With 8 × 103 cells/well, this peptide reduced cell growth at 100, 500, and 1000 nM. In conclusion, we suggest that these peptides may be potential and promising compounds for the treatment of dogs with simple carcinomas of the mammary gland. In vivo studies are required to confirm this hypothesis.

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Section: Discussionsupporting

confidence: 93%

Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

et al. 2016

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“…Years ago, we have reported that DDAVP can modulate both cell growth and secretion of the serine protease urokinase in cultures of mouse mammary tumor cells [46]. More recently, preliminary results indicated that treatment of MCF-7 monolayers with DDAVP, in the presence of proper concentrations of plasminogen, induced the formation of angiostatin, a natural, tumor-born inhibitor of angiogenesis [47].…”

Section: The Vasopressin Analog Ddavpmentioning

confidence: 99%

Metastasis: Recent Discoveries and Novel Perioperative Treatment Strategies with Particular Interest in the Hemostatic Compound Desmopressin

Alonso

Ripoll

Garona³

et al. 2011

CPB

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Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

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“…Several reports indicate that uPA expression can be up‐regulated in tumor cells by growth factors, including hepatocyte growth factor/scatter factor (HGF/SF; [52]), vascular endothelial growth factor (VEGF; [53]) epidermal growth factor (EGF; [48,49]), insulin‐like growth factors I and II (IGF‐I and IGF‐II; [54]), basic fibroblast growth factor (bFGF; [55]), lysophosphatidic acid (LPA; [56]), colony stimulating factor‐1 (CSF‐1; [57,58]), vasopressin [59], and thrombin [60], among others. Most of these exogenous signals, through their receptors, activate PLC, PKC, PLD, Ral, Ras, Raf, Mek‐1 and Erk1/2 [28,39,61] and also members of the Rho, Rac and Cdc42 family of small GTP‐binding proteins [46,62,63].…”

Section: Extracellular and Intracellular Signals Regulating The Produmentioning

confidence: 99%

Deregulation of the signaling pathways controlling urokinase production

Ghiso

Alonso

Farías

et al. 1999

European Journal of Biochemistry

175

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We review the evidence in support of the notion that, upon experimental oncogenic transformation or in spontaneous human cancers, mitogenesis and expression of urokinase (uPA) and its receptor (uPAR) are activated through common signaling complexes and pathways. It is well documented that uPA, uPAR or metalloproteinases (MMPs) are overexpressed in tumor cells of mesenchymal or epithelial origin and these molecules are required for tumor invasion and metastasis. Furthermore, oncogenic stimuli, which may render the transformed cells tumorigenic and metastatic in vivo, activate, in a constitutive fashion, the extracellular-regulated kinases (Erk 1 and 2) classical mitogenic pathway and others such as the NH(2)-Jun-kinase (Jnk). Cells from human tumors or oncogene-transformed cells overexpress uPA and uPAR, and also show a sustained activation of the above-mentioned signaling modules. In this paper we show that the classical mitogenic pathway involving Ras-Erk, PKC-Erk or Rac-JNK, among others, is activated by growth factors or endogenously by oncogenes, and constitutively activates uPA and uPAR expression. All the data obtained from human tumors or experimental systems, incorporated into a general model, indicate that oncogenic stimuli lead to the constitutive activation of mitogenesis and uPA and its receptor expression, through the activation of the same classical and nonclassical signaling complexes and pathways that regulate cell proliferation. We also discuss contrasting points of view. For instance, what governs the differential regulation of mitogenesis and the signal that leads to protease overexpression in a way that allows normal cells during physiological events to respond to growth factors, and proliferate without overexpressing extracellular matrix (ECM) proteases? Or how can cells remodel their microenvironment without proliferating? What restrains benign tumors from overexpressing tumor-associated proteases when they certainly have the mitogenic signal fully activated? This may occur by the differential regulation of transcriptional programs and recent reports reviewed in this paper may provide an insight into how this occurs at the signaling and transcriptional levels.

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Modulation of growth and urokinase secretion by vasopressin and closely related nonapeptides in metastatic mouse mammary tumor cells

Cited by 4 publications

References 0 publications

Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

Metastasis: Recent Discoveries and Novel Perioperative Treatment Strategies with Particular Interest in the Hemostatic Compound Desmopressin

Deregulation of the signaling pathways controlling urokinase production

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