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

Oncogene volume 20, pages 2032–2043 (2001)Cite this article

Abstract

Vitronectin (VN) and pro-urokinase (pro-uPA) stimulated migration of rat smooth muscle cells in a dose-dependent and additive way, and induced motile-type changes in cell morphology together with a complete reorganization of the actin filaments and of the microtubules. All these effects were inhibited by pertussis toxin, or by antibodies directed against the urokinase receptor (uPAR) or against the VN receptor αvβ3 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 VN-induced cell migration. On the other hand, PD 98059, an inhibitor of MEK, differentially inhibited the pro-uPA- but 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 different.

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Abbreviations

PI-3K:

phosphatidylinositol-3 kinase

PK-A:

protein kinase A

PK-C:

protein kinase C

pro-uPA:

pro-urokinase

PT:

pertussis toxin

RSMC:

rat smooth muscle cells

uPA:

urokinase

uPAR:

urokinase receptor

VN:

vitronectin.

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Acknowledgements

The authors thank Drs M Bertulli and MG Pizza for providing cells and reagents. We are very grateful to Drs N Johanson and A Mondino for helpful advice and comments. Supported by grants of the Italian Association for Cancer Research (AIRC), the Italian Ministry of University and of Scientific and Technological Research (MURST, PRIN 99), the Istituto Superiore di Sanità and the EU Fifth Framework Program (Contract QLG1-CT-2000-01131).

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  1. Bernard Degryse

    Present address: Department of Vascular Biology, The Scripps Research Institute, La Jolla, 92037, CA, USA

Authors and Affiliations

  1. Department of Molecular Pathology and Medicine, Università, Vita-Salute San Raffaele, Via Olgettina 58, 20132, Milano, Italy

    Bernard Degryse, Simone Orlando, Massimo Resnati & Francesco Blasi

  2. McGill University and Royal Victoria Hospital, 687 Pine Avenue West, Room H4-60, Montreal, H3A1A1, Quebec, Canada

    Shafaat A Rabbani

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Degryse, B., Orlando, S., Resnati, M. et al. Urokinase/urokinase receptor and vitronectin/αvβ3 integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways. Oncogene 20, 2032–2043 (2001). https://doi.org/10.1038/sj.onc.1204261

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