Migration of retinal pigment epithelium cells in vitro is regulated by protein kinase C

Murphy, Todd L.; Sakamoto, Taiji; Hinton, David R.; Spee, Christine; Gundimeda, Usha; Soriano, Danilo Sone; Gopalakrishna, R.; Ryan, Stephen J.

doi:10.1016/s0014-4835(05)80010-7

Cited by 49 publications

(41 citation statements)

References 46 publications

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“…Here we show that the negative effect of n-butanol on LM3 cell spreading was completely reversed by the presence of PMA, suggesting that, in the sequence of events leading to the activation of PKC, n-butanol was acting at the same or earlier stages than PMA. Enhancement of cell spreading and motility by TPA or PMA have been recently described in other models of tumor and normal cells (Vuori and Ruoslahti, 1993;Murphy et al, 1995) although no association has been established with PLD participation.…”

Section: Discussionmentioning

confidence: 91%

A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and β1-integrin point contact distribution

et al. 1997

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Spreading is a critical process involved in motility and growth of tumor cells during the metastatic cascade. Focal adhesion kinase, src-proteins and PKC have been reported to participate in the regulation of cytoskeleton organization in both normal and transformed cells during spreading. The role of other signaling enzymes such as PLD and PAP has not been studied during spreading in tumor cells. We now show that the spreading of murine mammary adenocarcinoma LM3 cells was significantly reduced by n-butanol, a PLD and PKC inhibitor, with a maximal inhibition of 54% (p F 0.001) in both the presence and absence of serum, as measured by phasecontrast microscopy. PMA only stimulated cell spreading over the control in the absence of serum and n-butanol inhibition was completely reversed by PMA treatment in both conditions. PA, the product of PLD activity, stimulated LM3 cell spreading and the same effect was observed with staurosporine. Spreading was enhanced when cells were seeded on collagen-IV-or fibronectin-coated surfaces and n-butanol could inhibit both integrin-derived signals. Focal adhesion and spreading are critical processes for morphology, anchorage, motility and growth of tumor cells (Hao Lo and Bo Chen, 1994). The interaction of tumor cells with components of the extracellular matrix (ECM) such as fibronectin (FN), collagen (CL) or laminin has been described as a key mechanism in metastasis formation (Juliano, 1994;Brodt, 1996). Within the final steps of the metastatic cascade, tumor cells, after binding to the endothelium of the target organ, have to adhere, spread and migrate on specific components of the ECM and basement membrane, in order to extravasate and develop metastatic foci (Brodt, 1996). However, it is not clear which are the effector molecules and signaling pathways regulating tumor-cell adhesion and spreading required for motility during different stages of the metastatic cascade.

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Section: Discussionmentioning

confidence: 91%

A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and β1-integrin point contact distribution

et al. 1997

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“…Both integrins are also present in the RPE [25, 26], and it may be possible that thalidomide modulates RPE cell growth in a similar pattern as endothelial cell growth. Our finding that PDGF-induced cell proliferation – which is also PKC-dependent [27, 28]– is blocked by thalidomide implies that PKC may be a key regulator and the main target of thalidomide. More detailed information on the mechanisms of thalidomide-induced inhibition of cellular proliferation cannot be provided since there is no knowledge about detailed ways of signal transduction and intracellular mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide and Prednisolone Inhibit Growth Factor-Induced Human Retinal Pigment Epithelium Cell Proliferation in vitro

Kaven

Spraul²,

Zavazava³

et al. 2001

Ophthalmologica

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Thalidomide and prednisolone were recently introduced as treatment modalities in age-related macular degeneration (AMD). Growth factor-induced activation of retinal pigment epithelial (RPE) cells is a crucial event in this disease. The purpose was to examine the effect of thalidomide and prednisolone on growth factor-preactivated RPE cells. Human RPE cells were stimulated with 10 ng/ml platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), or vascular endothelial growth factor (VEGF) for 24 h. Afterwards, thalidomide (50 µg/ml) or prednisolone (100 ng/ml) were added for 24 h. RPE cell proliferation was determined by [³H]-thymidine incorporation. PDGF and bFGF significantly stimulated human RPE cell proliferation (p < 0.005), the value for VEGF stimulation was not significant (p = 0.3). The effect of the growth factors was diminished after addition of thalidomide and prednisolone (p < 0.005). The current study shows that the inhibitory properties of thalidomide and prednisolone remain even after growth factor activation of the cells.

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“…For stimulation of PKC, RPE cells were treated with phorbol ester (phorbol 12-myristate 13-acetate, PMA, Sigma; 100 n M ) for 1 h. It was also reported that the short exposure of RPE cells to PMA (1 h) stimulated the activity of PKC [3]. HA-1004 (LC Laboratories, 100 n M ) was used as a negative control for calphostin C, and 4α-phorbol 12,13-didecanoate (Sigma) was used as a negative control for PMA [3]. …”

Section: Methodsmentioning

confidence: 99%

“…Although much effort has been concentrated on the study of SRN, its pathogenesis is still unknown and no effective therapy has been found. Pathologic study of SRN has shown that retinal pigment epithelium (RPE) cells and choroidal endothelial cells are intermingled in choroid-retinal tissue [2, 3, 4]. Among these, the RPE cells are believed to have a major effect in modulating SRN and retinal degeneration, both in progression and in regression [2, 3, 5].…”

Section: Introductionmentioning

confidence: 99%

Interferon β Affects Retinal Pigment Epithelial Cell Proliferation via Protein Kinase C Pathways

et al. 2001

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Background: The aim of this study is to see the effect of interferon β (IFN-β) on cell proliferation and the protein kinase C (PKC) signaling pathway. Methods: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-β, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-β were assessed by ³H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-β and calphostin C was also measured.Results: IFN-β inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and ³H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-β had no inhibitory or stimulatory effect on ³H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-β exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. Conclusion: IFN-β inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.

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Migration of retinal pigment epithelium cells in vitro is regulated by protein kinase C

Cited by 49 publications

References 46 publications

A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and β1-integrin point contact distribution

A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and β1-integrin point contact distribution

Thalidomide and Prednisolone Inhibit Growth Factor-Induced Human Retinal Pigment Epithelium Cell Proliferation in vitro

Interferon β Affects Retinal Pigment Epithelial Cell Proliferation via Protein Kinase C Pathways

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