Selective localization of receptors for urokinase amino-terminal fragment at substratum contact sites of an in vitro-established line of human epidermal cells

Rosso, Mario Del; Pedersen, Nina Marie; Fibbi, Gabriella; Pucci, Marco; Dini, Germana; Anichini, E; Blasi, Francesco

doi:10.1016/0014-4827(92)90017-3

Cited by 19 publications

(21 citation statements)

References 22 publications

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“…In addition to their direct involvement in the proteolytic (uPAR) and adhesive properties of cells, both pro-uPA (Gudewicz and Bilboa, 1987; Boyle et Fibbi et al, 1988;Del Rosso et al, 1992;Resnati et al, 1996;Gyetko et al, 1996;Degryse et al, 1999) and VN (Yebra et al, 1996;Kjùller et al, 1997;Stahl and Mueller, 1997;Carriero et al, 1999; directly stimulate cell migration. The interaction of uPAR with several integrins and the modulation of their function is an established fact; for example, the presence and the level of uPAR a ects the choice between adhesion on ®bronectin v. vitronectin, the internalization of ®brinogen or even the constitutive activation of MAP-K in certain cancer cells leading to cell proliferation Simon et al, 1996;Xue et al, 1997;Dumler et al, 1999;Aguirre Ghiso et al, 1999;Kusch et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Urokinase/urokinase receptor and vitronectin/αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways

et al. 2001

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Vitronectin (VN) and pro-urokinase (pro-uPA) stimulated migration of rat smooth muscle cells in a dosedependent and additive way, and induced motile-type changes in cell morphology together with a complete reorganization of the actin ®laments and of the microtubules. All these e ects were inhibited by pertussis toxin, or by antibodies directed against the urokinase receptor (uPAR) or against the VN receptor a v b 3 suggesting that an association between the two receptors is required to mediate both signals. Investigation of the signaling pathways showed that increasing the intracellular cAMP resulted in a selective inhibition of VNinduced cell migration. On the other hand, PD 98059, an inhibitor of MEK, di erentially inhibited the pro-uPAbut not the VN-induced cell migration. Phosphorylation and nuclear translocation of Erk by pro-uPA was directly observed. We conclude that the signaling pathways of pro-uPA and VN must be at least in part di erent. Oncogene (2001Oncogene ( ) 20, 2032Oncogene ( ± 2043

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Section: Discussionmentioning

confidence: 99%

Urokinase/urokinase receptor and vitronectin/αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways

et al. 2001

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“…Conversely, most binding sites specifically concentrated in membrane remnants remaining on the culture dish after exhaustive detachment of cells with EDTA (material referred to as surface-attached material [SAM]). Such SAM was previously shown to consist mainly of microvesicles with a typical bilayer conformation, to possess typical markers of cell focal contacts, and to concentrate about 50% of total u-PAR 36,37 ) (lane 5).…”

Section: Thementioning

confidence: 96%

“…3) The receptor was anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor, because treatment with GPI-specific phospholipase C, per-formed on SAM as previously described, 36 could release u-PAR (lane 6).…”

Section: Thementioning

confidence: 99%

Functions of the Fibrinolytic System in Human Ito Cells and Its Control by Basic Fibroblast and Platelet–Derived Growth Factor

et al. 1999

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“…Cells were then centrifuged, and the pellet was lysed in lysis buffer (partial cell lysate). The combined trypsin/EDTA treatment leaves a complex material, referred to as surface-adherent material (24), on the culture dish, which primarily represents the cell focal contacts and is enriched with uPAR. Thus, the partial cell lysate was replaced in the culture dish for 1 h at 4°C to lyse the surface-adherent material-associated uPAR (total cell lysate) as well.…”

Section: Cell Lines and Cell Cultures-m14 Human Melanoma Cells Mcf7mentioning

confidence: 99%

bcl-2 Induction of Urokinase Plasminogen Activator Receptor Expression in Human Cancer Cells through Sp1 Activation

Trisciuoglio¹,

Iervolino²,

Candiloro³

et al. 2004

Journal of Biological Chemistry

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We have previously demonstrated that Bcl-2 overexpression in human breast carcinoma and melanoma cells synergizes with hypoxia to increase angiogenesis through up-regulation of vascular endothelial growth factor. In this work we demonstrated, for the first time, that Bcl-2 overexpression in cancer cells exposed to hypoxia modulates urokinase plasminogen activator receptor (uPAR) expression through Sp1 transcription factor and that the extracellular signal-regulated kinase (ERK) pathway plays a role in Sp1 transcriptional activity. In particular, an increase in uPAR protein and mRNA expression was found in melanoma bcl-2 transfectants grown under hypoxia when compared with control cells, and a decrease of uPAR protein expression was induced by treatment of cells with specific bcl-2 antisense oligonucleotides. Up-regulation of uPAR expression was accompanied by increased Sp1 protein expression, stability, serine phosphorylation, and DNA binding activity. Treatment of cells with mitramycin A, an inhibitor of Sp1 activity, confirmed the role of Sp1 transcriptional activity in uPAR induction by Bcl-2. The contribution of the ERK pathway in Sp1-increased transcriptional activity was demonstrated by the use of chemical inhibition. In fact, ERK kinase activation was induced in Bcl-2-overexpressing cells exposed to hypoxia, and the ERK kinase inhibitor UO126 was able to down-regulate Sp1 phosphorylation and DNA binding activity. Using a human breast carcinoma line, we obtained data supporting our findings with melanoma cells and identified a link between the induction of Sp1 and uPAR expression as a common bcl-2-controlled phenomenon in human tumors. In conclusion, our results strongly indicate that up-regulation of uPAR expression by Bcl-2 in hypoxia is modulated by Sp1 DNA binding activity through the ERK signaling pathway.Angiogenesis is a fundamental process required for tumor growth, invasion, and metastasis and is strongly induced by hypoxia. In fact, several cell types including tumor cells, macrophages, and endothelial cells respond to hypoxia by producing angiogenic factors, fibrinolytic factors, and adhesion molecules involved in pathologic angiogenesis (1-5). Four sequential steps can be distinguished during angiogenesis: the degradation of the basement membrane and interstitial matrix, endothelial cell migration, endothelial cell proliferation, and the formation of tubular structures with a lumen and a new basement membrane (6). Three of these steps critically depend on proteolytic activity generated by the matrix metalloproteinases and the plasminogen activator/plasmin system. In particular, the role of urokinase plasminogen activator receptor (uPAR) 1 in tumor cell invasion and migration and in the formation of new microvascular structures has been largely demonstrated (7-9).Angiogenesis is also controlled by alterations in oncogene and tumor suppressor gene expression (10 -14). In this context, we previously demonstrated that the bcl-2 oncogene increases in vitro and in vivo angiogenesis in two different t...

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Selective localization of receptors for urokinase amino-terminal fragment at substratum contact sites of an in vitro-established line of human epidermal cells

Cited by 19 publications

References 22 publications

Urokinase/urokinase receptor and vitronectin/αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways

Urokinase/urokinase receptor and vitronectin/αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways

Functions of the Fibrinolytic System in Human Ito Cells and Its Control by Basic Fibroblast and Platelet–Derived Growth Factor

bcl-2 Induction of Urokinase Plasminogen Activator Receptor Expression in Human Cancer Cells through Sp1 Activation

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