Cause of separation of the lymphatic system discovered
(Vienna, 21 Jan. 2011) By deciphering the mechanism for separating the lymphatic system from the vascular system researchers from MedUni Vienna are answering a previously unsolved question of developmental biology and medicine. This may also lead to a new approach for suppressing the metastasis of tumours.
The human lymph vessel system is not only a key component of the immune system, it is also necessary for maintaining the balance of fluids in the tissue and absorbing fats in the digestive tract, and it plays an essential role in the metastasis of tumours.
On its origins it is known that the lymphatic vessels develop from embryonic veins as certain endothelial cells of the cardinal veins start to produce lymphatic marker proteins (e.g. Prox-1 or podoplanin). At these “marked” places there is then the growth of endothelial cells and formation of so-called lymph sacs, from which the peripheral lymphatic vessels subsequently develop. A key step in this process is ultimately the separation of the newly formed lymph sacs from the cardinal veins, and the mechanism responsible for this was largely unclear until now.
DI Dr. Pavel Uhrin and Dr. Jan Zaujec from the Institute of Vascular Biology at MedUni Vienna have been able to prove for the first time that this separation of the lymphatic system from the blood-carrying vessels is caused by the activation of thrombocytes (platelets; smallest cells of the blood) which is triggered by the marker protein podoplanin. If the effect of podoplanin is suppressed or thrombocyte activation is inhibited, complete separation does not take place and there remains a mixture between blood and lymph.
Since podoplanin is also formed on the surface of tumour cells, the podoplanin-induced activation of the thrombocytes could also be an important mechanism for the growth of tumour cells and the metastasis of tumours. This means suppressing the interactions between podoplanin and thrombocytes using blocking antibodies may be a possible therapeutic approach to prevent the progression and/or metastasis of tumour cells.
These fundamental findings of the researchers headed by Uhrin and Zaujec have also been published as a cover story in the top scientific journal BLOOD. They were discovered mainly at the Institute of Vascular Biology and Thrombosis Research at MedUni Vienna in cooperation with Univ. Prof. Dr. Dontscho Kerjaschki (Head of the Clinical Institute of Pathology at MedUni Vienna), who also initiated this study. Kerjaschki is an expert recognised worldwide in the field of the lymphatic system and in previous studies had discovered and characterised podoplanin as a selective marker of lymphatic vessels which does not appear in blood vessels.
DI Dr. Pavel Uhrin, born in 1961, studied physical and analytical chemistry in Bratislava and worked at the Institute of Animal Breeding in Nitra, Slovakia. After finishing his dissertation in the subject of biochemistry in 1989 he completed a three-year research stay as a postdoctoral fellow in the USA (College of Medicine, Cincinnati). Since then he has worked at the Institute of Vascular Biology and Thrombosis Research. In 2000 he qualified as a professor in Nitra. Uhrin is Head of the Transgenic Animal Core Facility (TACF) at the Institute of Vascular Biology and Thrombosis Research and in this capacity he has been involved in the development of knockout mice. At the time, the protein C inhibitor knockout mouse was the first knockout mouse developed at the University of Vienna, and this successfully stimulated research activities in this field.
Mag. Vet. Med. Dr. Jan Zaujec, born in 1972, studied veterinary medicine in Kosice and worked at the Institute of Animal Breeding in Nitra, Slovakia. In 2000 while still a doctoral student he joined the group of Dr. Uhrin at the Medical University of Vienna and in 2005 qualified as a doctor of “General animal sciences and biotechnology” in Nitra. From 2006 to 2007 he worked at the State Veterinary Medicine Institute, Department of Pathology, in Nitra, Slovakia.
At the Institute of Vascular Biology and Thrombosis Research he developed the technique of aggregation of homologous recombination, embryonic stem cell clones in order to generate chimeric mice and subsequently knockout mice. As a trained surgeon he also established several techniques for characterising the phenotype of knockout mice (e.g. carotic artery ligation model, femoral artery cuff model, Matrigel plug assay). As well as the analysis of the phenotype of the podoplanin knockout mice Dr. Zaujec was also heavily involved in a project in which ISG12 knockout mice were generated and characterised.
„Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation”
Pavel Uhrin, Jan Zaujec, Johannes M. Breuss, Damla Olcaydu, Peter Chrenek, Hannes Stockinger, Elke Fuertbauer, Markus Moser, Paula Haiko, Reinhard Fässler, Kari Alitalo, Bernd R. Binder, and Dontscho Kerjaschki