Secretion of Cytokines by Human Choroidal Melanoma Cells and Skin Melanoma Cell Lines in vitro

Enzmann, Volker; Faude, Frank; Kohen, Leon; Wiedemann, Peter

doi:10.1159/000055473

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…Recently, we demonstrated that choroidal melanoma cells secrete a variety of cytokines in vitro [6]. Interestingly, the secretion of IL-6 and IL-8, both known as proinflammatory factors, is strongly up-regulated in malignant melanoma cell lines and in choroidal melanoma cell cultures.…”

Section: Discussionmentioning

confidence: 99%

Alterations of sensory retinal explants exposed to choroidal melanoma cells ex vivo

Enzmann¹,

Germer

Francke

et al. 2000

Graefe's Archive for Clinical and Experimental Ophthalmology

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Section: Discussionmentioning

confidence: 99%

Alterations of sensory retinal explants exposed to choroidal melanoma cells ex vivo

Enzmann¹,

Germer

Francke

et al. 2000

Graefe's Archive for Clinical and Experimental Ophthalmology

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“…After injury to the choroid/retina, RPE cells are exposed to a variety of growth factors and cytokines from the serum, resulting in cell proliferation. RPE cell proliferation is an important step in the pathogenesis of retinal diseases, such as proliferative vitreoretinopathy (PVR), and may be associated with choroidal melanoma which lead to impairment or even loss of vision (Enzmann et al, 1998). Nothing is known about the signalling and the molecular mechanisms underlying these processes and we still know very little about the intracellular signalling that mediates RPE cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

cAMP inhibits the proliferation of retinal pigmented epithelial cells through the inhibition of ERK1/2 in a PKA-independent manner

et al. 2002

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Retinal pigmented epithelial (RPE) cell integrity is critical to the maintenance of retina functions and RPE cells do not proliferate in adults. The activation of RPE results in cell proliferation which may be associated with proliferative retinopathy and choroidal melanoma. Mitogen-activated protein kinase (MAPK) is believed to be a key participant in the response to mitogenic stimuli. We therefore investigated the involvement of the extracellular signal-regulated protein kinase (ERK) 1 and 2 during the induction of RPE cell proliferation. After foetal calf serum (FCS) stimulation activation of the Ras/Raf/ERK signalling pathway was detected by Western blotting and immunochemistry, with specific anti-phosphosignalling protein antibodies. Pharmacological and antisense (AS) oligonucleotide (ODN) strategies were used to analyse the signalling involved in FCS-induced RPE cell proliferation. Activation of the small G protein Ras and, to a lesser extent of Raf-1, the kinase directly downstream from Ras, was necessary to FCS-induced cell proliferation. MEK1/2 and ERK1/2 were activated during cell proliferation. Inhibition of MEK1/2 with UO 126 completely abolished ERK1/2 activation and reduced cell proliferation by 33 -43%. ERK1/2 depletion by an AS ODN approach reduced cell proliferation by 27 -33%, confirming the role of ERK1/ 2 in the FCS stimulation of RPE cells. We also investigated the role of PKA/cAMP, one of the major inhibitory pathways of ERK1/2. PKA blockade did not modify ERK1/2 activation or cell proliferation. In contrast, agents that increased cAMP concentration, abolished RPE proliferation, and MEK/ERK activation. Moreover, inhibition of the cAMP-activated small G protein Rap1, partially reversed the inhibitory effects of cAMP on cell proliferation and MEK/ERK activation. The requirement for Ras and ERK1/2, the lack of ERK1/2 regulation by PKA and the cAMP/Rap1 counter-regulatory pathway for ERK-mediated cell proliferation suggest complex regulation of signalling in RPE cells. These data may have important implications for the development of more selective models for retinal anti-proliferative therapies.

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“…In vivo, despite the presence of FGF2 in the retinal interphotoreceptor matrix, retinal pigmented epithelial (RPE) cells have a limited proliferation capacity, corresponding to the normal increase in retinal space associated with growth and age. Increased levels of FGF2 with elevated levels of FGF2 excretion have been detected in cells derived from pigment cell tumors and RPE-associated choroidal melanomas in humans (Enzmann et al, 1998). Although RPE cells are unable to divide in vivo, they may still require survival factors to inhibit their apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Both FGF1 and Bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2

Bryckaert

Guillonneau²,

Hecquet³

et al. 1999

Oncogene

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Retinal pigmented epithelial (RPE) cells are of central importance in the maintenance of neural retinal function. Changes in the RPE cells associated with repair activities have been described as metaplasia, while RPE cell apoptosis is responsible for the development of a variety of retinal degenerations. We investigated the regulation of the anti-apoptotic properties of the ®broblast growth factors (FGF) 2 in serum-free cultures of RPE cells. In the absence of serum, con¯uent stationary RPE cells died by apoptosis via a caspase 3-dependent pathway. The addition of FGF2 greatly reduced apoptosis over a 7-day culture period. We demonstrated the involvement of an autocrine loop involving endogenous FGF1 in the mechanisms that govern FGF2-induced resistance to apoptosis by showing: (1) higher levels of apoptosis in cells treated with antisense FGF1 oligonucleotide or after neutralization of excreted FGF1; (2) the long-term activation of FGFR1 and of ERK2, (3) the inhibition of FGFR1 and ERK2 activation and an increase in apoptosis if excreted FGF1 was neutralized. FGF2 also increased the de novo synthesis and the production of Bcl-xl before the onset of apoptosis. Both inhibition of ERK2 activation, which decreased Bcl-xl synthesis, and downregulation of Bcl-x by antisense oligonucleotide treatment inhibited the survival-promoting activity of FGF2. Thus, FGF2-induced cell survival is a progressive adaptive phenomenon involving ERK2 activation by excreted FGF1 and ERK2-dependent Bcl-x production.

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Secretion of Cytokines by Human Choroidal Melanoma Cells and Skin Melanoma Cell Lines in vitro

Cited by 7 publications

References 24 publications

Alterations of sensory retinal explants exposed to choroidal melanoma cells ex vivo

Alterations of sensory retinal explants exposed to choroidal melanoma cells ex vivo

cAMP inhibits the proliferation of retinal pigmented epithelial cells through the inhibition of ERK1/2 in a PKA-independent manner

Both FGF1 and Bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2

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