Evidence for Control of Nitric Oxide Synthesis by Intracellular Transforming Growth Factor-β1 in Tumor Cells

Lagadec, Patricia; Raynal, Stéphane; Lieubeau, Blandine; Onier, Nathalie; Arnould́, Laurent; Saint-Giorgio, Valérie; Lawrence, David A.; Jeannin, Jean–François

doi:10.1016/s0002-9440(10)65444-2

Cited by 22 publications

(21 citation statements)

References 39 publications

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“…Interestingly, similar observations were made in another tumor system, in which induction of tumor regression by bacterial products was associated with a decrease in TGF -1 and an increase in NO in tumors. 56,57 It is noteworthy that orthotopic PC3MM2 tumors were more susceptible to AdIFN -therapy than were their subcutaneous counterparts. Although it is not clear what caused this differential susceptibility, this observation cautions that experimental therapeutic studies for prostate cancer should be performed in the orthotopic organ.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated interferon-β gene therapy suppresses growth and metastasis of human prostate cancer in nude mice

Cao

Wang

et al. 2001

Cancer Gene Ther

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The purpose of this study was to determine the effects of interferon -(IFN -) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN -( AdIFN -) , but not a vector encoding bacterial -galactosidase ( AdLacZ ) , suppressed PC3MM2 tumors in a dose -dependent manner. At the highest dose ( 2Â10 9 plaque -forming units, PFU ) , a single injection of AdIFN -( but not AdLacZ ) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN -± treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN -expressed higher levels of IFN -and inducible nitric oxide synthase ( iNOS ) and lower levels of basic fibroblast growth factor ( bFGF ) and transforming growth factor 1 ( TGF -1). In vitro analysis indicated that expression of bFGF and TGF -1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN -gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN -correlated with up -regulation of iNOS and down -regulation of angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated interferon-β gene therapy suppresses growth and metastasis of human prostate cancer in nude mice

Cao

Wang

et al. 2001

Cancer Gene Ther

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“…Both high salt intake and high glucose also enhance NO synthesis (Ying & Sanders, 1999;Trachtman et al, 1998), whereas NO blocks TGF-b synthesis and suppresses matrix protein synthesis by mesangial cells (Craven et al, 1997;Studer et al, 1999). Conversely, TGF-b inhibits NO synthesis in mesangial cells (Koide et al, 1994;Lagadec et al, 1999). However, in skeletal muscle and endothelial cells, TGF-b enhanced NO synthesis.…”

Section: Transforming Growth Factor-b No and Hypertensionmentioning

confidence: 99%

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

Das¹

2004

Eur J Clin Nutr

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Patients with uncontrolled essential hypertension have elevated concentrations of superoxide anion (O 2 ÀK ), hydrogen peroxide (H 2 O 2 ), lipid peroxides, endothelin, and transforming growth factor-b (TGF-b) with a simultaneous decrease in endothelial nitric oxide (eNO), superoxide dismutase (SOD), vitamin E, and long-chain polyunsaturated fatty acids (LCPUFAs). Physiological concentrations of angiotensin II activate NAD(P)H oxidase and trigger free radical generation (especially that of O 2 ÀK ). Normally, angiotensin II-induced oxidative stress is abrogated by adequate production and release of eNO, which quenches O 2 ÀK to restore normotension. Angiotensin II also stimulates the production of endothelin and TGF-b. TGF-b enhances NO generation, which in turn suppresses TGF-b production. Thus, NO has a regulatory role on TGF-b production and is also a physiological antagonist of endothelin. Antihypertensive drugs suppress the production of O 2 ÀK and TGF-b and enhance eNO synthesis to bring about their beneficial actions. LCPUFAs suppress angiotensin-converting enzyme (ACE) activity, reduce angiotensin II formation, enhance eNO generation, and suppress TGF-b expression. Perinatal supplementation of LCPUFAs decreases insulin resistance and prevents the development of hypertension in adult life, whereas deficiency of LCPUFAs in the perinatal period results in raised blood pressure later in life. Patients with essential hypertension have low concentrations of various LCPUFAs in their plasma phospholipid fraction. Based on this, it is proposed that LCPUFAs serve as endogenous regulators of ACE activity, O 2 ÀK , eNO generation, and TGF-b expression. Further, LCPUFAs have actions similar to statins, inhibit (especially o-3 fatty acids) cyclooxygenase activity and suppress the synthesis of proinflammatory cytokines, and activate the parasympathetic nervous system, all actions that reduce the risk of major vascular events. Hence, it is proposed that availability of adequate amounts of LCPUFAs during the critical periods of growth prevents the development of hypertension in adulthood.

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“…Progressive colon carcinoma cells (PROb cells) secreting active TGFb had the ability to inhibit cytokine-induced NO production in EC219 endothelial cells and microglial cells while a regressive clone (REGb cells) isolated from the same carcinoma but secreting only latent TGFb did not display these properties [14]. In PROb cells, regulation of NO secretion by TGFb was an intracrine process, whereas exogeneously added TGFb was ineffective [24]. The activation of latent TGFb has been shown to be mediated by direct contact between endothelial and smooth muscle cells [25].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Interaction Between TGF β and Nitric Oxide in the Mechanisms of Progression of Colon Carcinoma

Lohm

Peduto-Eberl

Lagadec

et al. 2005

Clin Exp Metastasis

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It is recognised that stromal cells determine cancer progression. We have previously shown that active TGFbeta produced by rat colon carcinoma cells modulated NO production in rat endothelial cells. To elucidate the role of TGFbeta and NO in the mechanisms of interaction of colon carcinoma cells with stromal cells and in cancer progression, we transfected REGb cells, a regressive colon carcinoma clone secreting latent TGFbeta, with a cDNA encoding for a constitutively-secreted active TGFbeta. Out of 20 injected rats only one tumour progressed, which was resected and sub-cultured (ReBeta cells). ReBeta cells secreted high levels of active TGFbeta. The adhesive properties of REGb and Rebeta cells to endothelial cells were similar, showing that the secretion of active TGFbeta is not involved in tumour cell adhesion to endothelial cells. ReBeta, but not REGb, cell culture supernatants inhibited cytokine-dependent NO secretion by endothelial cells, but inhibition of NO production was similar in co-cultures of REGb or ReBeta cells with endothelial cells. Therefore, secretion of active TGFbeta regulated endothelial NO synthase activity when tumour cells were distant from, but not in direct contact with, endothelial cells. However, only ReBeta cells inhibited cytokine-dependent secretion of NO in coculture with macrophages, indicating that the active-TGFbeta-NO axis confers an advantage for tumour cells in their interaction with macrophages rather than endothelial cells in cancer progression.

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Evidence for Control of Nitric Oxide Synthesis by Intracellular Transforming Growth Factor-β1 in Tumor Cells

Cited by 22 publications

References 39 publications

Adenovirus-mediated interferon-β gene therapy suppresses growth and metastasis of human prostate cancer in nude mice

Adenovirus-mediated interferon-β gene therapy suppresses growth and metastasis of human prostate cancer in nude mice

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

Evaluation of the Interaction Between TGF β and Nitric Oxide in the Mechanisms of Progression of Colon Carcinoma

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