For some cells, it is necessary to migrate within the body. This applies, for example, for angiogenic endothelial cells or immune cells the latter for detecting intruders as well as tumor cells to defense the body. Tumor cells often employ the same mechanism as these cells or “hijack" them to penetrate tissues and form metastases. A major component of this migration mechanism is the urokinase plasminogen activator (uPA) and a specific receptor (sM6P/IGF2R, CD222) that regulates the functions of uPA.
In an interdisciplinary study, Dr. Vladmir Leksa has now shown that by means of a peptide derived from M6P/IGF2R, he can selectively inhibit the uPA system. In in vitro tests not only the migration of angiogenic endothelial cells and the infiltration of cancer cells in artificial tissues was inhibited, but also in vivo in experimental animals the growth of human melanoma cells. This is the basis to develop new therapeutic approaches to suppress tumor growth and metastasis.
The work of Dr. Vladimir Leksa was performed in cooperation with the Center for Physiology and Pharmacology, the University Hospital of Dermatology and Internal Medicine I, Medical University of Vienna and the Institute of Molecular Biology, Slovak Academy of Sciences.
Inhibition of migration of endothelial cells (green) in an artificial tissue in the mouse by the M6P/IGF2R peptide (right) in comparison to a control peptide (left)
Publication in „Circulation Research“: Soluble M6P/IGF2R released by TACE controls angiogenesis via blocking plasminogen activation. Vladimir Leksa, Robert Loewe, Brigitte Binder, Herbert B. Schiller, Paul Eckerstorfer, Florian Forster, Ana Soler Cardona, Gabriela Ondrovičová, Eva Kutejová, Eva Steinhuber, Johannes Breuss, Johannes Drach, Peter Petzelbauer, Bernd R. Binder †, Hannes Stockinger doi: 10.1161/CIRCRESAHA.110.234732
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