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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Osteosarcoma cells induce endothelial cell proliferation during neo-angiogenesis
Journal of Cellular Physiology, Volume 228, No. 4, Year 2013
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Description
Understanding the mechanisms inducing endothelial cell (EC) proliferation following tumor microenvironment stimuli may be important for the development of antiangiogenic therapies. Here, we show that cyclin-dependent kinase 2 and 5 (Cdk2, Cdk5) are important mediators of neoangiogenesis in in vitro and in vivo systems. Furthermore, we demonstrate that a specific Yin Yang 1 (YY1) protein-dependent signal from osteosarcoma (SaOS) cells determines proliferation of human aortic endothelial cells (HAECs). Following tumor cell stimuli, HAECs overexpress Cdk2 and Cdk5, display increased Cdk2 activity, undergo enhanced proliferation, and form capillary-like structures. Moreover, Roscovitine, an inhibitor of Cdks, blunted overexpression of Cdk2 and Cdk5 and Cdk2 activity induced by the YY1-dependent signal secreted by SaOS cells. Furthermore, Roscovitine decreased HAEC proliferation and angiogenesis (the latter by 70% in in vitro and 50% in in vivo systems; P<0.01 vs. control). Finally, the finding that Roscovitine triggers apoptosis in SaOS cells as well as in HAECs by activating caspase-3/7 indicates multiple mechanisms for the potential antitumoral effect of Roscovitine. Present work suggests that Cdk2 and Cdk5 might be pharmacologically accessible targets for both antiangiogenic and antitumor therapy. © 2012 Wiley Periodicals, Inc.
Authors & Co-Authors
de Nigris, Filomena
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Mancini, Francesco Paolo
Italy, Benevento
Università Degli Studi Del Sannio
Schiano, Concetta
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Infante, Teresa
Italy, Naples
Irccs Fondazione Sdn
Zullo, Alberto
Italy, Benevento
Università Degli Studi Del Sannio
Minucci, Pellegrino Biagio
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Al-Omran, Mohammed A.
Saudi Arabia, Riyadh
College of Medicine
Giordano, Antonio V.
Italy, Siena
Università Degli Studi Di Siena
United States, Philadelphia
Temple University
Napoli, Claudio
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Italy, Naples
Irccs Fondazione Sdn
Statistics
Citations: 31
Authors: 9
Affiliations: 6
Identifiers
Doi:
10.1002/jcp.24234
ISSN:
00219541
e-ISSN:
10974652
Research Areas
Cancer