The tumor - vessel interface constitutes a fragile
interaction system that is associated with continuous
tissue remodelling including cell invasion,
proliferation and apoptosis regulated by humoral and
cellular mediators. Tumor burden in patients has been
correlated with a hypercoagulable state and
thromboembolic complications, yet, any insights into
causal relations or molecular mechanisms are missing. We
have recently identified extracellular RNA (eRNA) as a
novel procoagulant co-factor for serine proteases and
eRNA promotes the initiation and progression of blood
coagulation in vivo. On the other hand, RNase
administration had a potent antithrombotic effect in
animal models of thrombosis. Moreover, both natural and
artificial eRNA lead to activation of endothelial cells.
Based on these findings, we hypothesize that eRNA plays
an important but yet unrecognized role in humoral and
cellular activities within the tumor - vessel interface.
In this project, we aim to (a) characterize eRNA in
association with tumor tissue entities and analyse
tumor-specific eRNA; (b) analyse the expression and
function of RNases in tumor and endothelial cells; (c)
characterize eRNA-dependent cellular activities of tumor
cells (proliferation, migration) and endothelial cells (permeability,
angiogenesis) as well as identify eRNA-dependent
receptor/signaling pathways; (d) describe the mechanism
of eRNA-related tumor-associated hypercoagulability in
different tumor models, and pursue the concept that
RNases may serve as novel anti-tumor modality. Results
from these proposed in vivo and in vitro experiments wil
gain novel insights into eRNA-dependent molecular and
cellular interrelations of the tumor - vessel interface
with the possibility to apply promising strategies for
tumor therapy. |
Chavakis T,
Athanasopoulos A, Rhee JS, Orlova V, Schmidt-Woll T,
Bierhaus A, May AE, Celik I, Nawroth PP, Preissner KT:
Angiostatin is a novel anti-inflammatory factor by
inhibiting leukocyte recruitment. Blood 105: 1036-43,
2005
Baal N, Reisinger K, Jahr
H, Bohle RM, Liang O, Munstedt K, Rao CV, Preissner
KT, Zygmunt MT: Expression of transcription
factor Oct-4 and other embryonic genes in CD133 positive
cells from human umbilical cord blood. Thromb Haemost
92: 767-75, 2004
Chavakis T, Keiper T,
Matz-Westphal R, Hersemeyer K, Sachs UJ, Nawroth PP, Preissner KT, Santoso S: The junctional adhesion
molecule-C promotes neutrophil transendothelial
migration in vitro and in vivo. J Biol Chem 279:
55602-8, 2004
Liang OD, Korff T,
Eckhardt J, Rifaat J, Baal N, Herr F, Preissner KT, Zygmunt MT: Oncodevelopmental alpha-fetoprotein
acts as a selective proangiogenic factor on endothelial
cell from the fetomaternal unit. J Clin Endocrinol Metab
89: 1415-22, 2004
Herr F, Liang OD, Herrero
J, Lang U, Preissner KT, Han VK, Zygmunt MT:
Possible angiogenic roles of insulin-like growth factor
II and its receptors in uterine vascular adaptation to
pregnancy. J Clin Endocrinol Metab 88: 4811-7, 2003
Chavakis T, Preissner
KT: Potential pharmacological applications of the
antithrombotic molecule high molecular weight kininogen.
Curr Vasc Pharmacol 1: 59-64, 2003
Rhee JS, Black M,
Schubert U, Fischer S, Morgenstern E, Hammes HP, Preissner KT: Potential pharmacological applications
of the antithrombotic molecule high molecular weight
kininogen. Curr Vasc Pharmacol 1: 59-64, 2003
Zygmunt MT, Herr
F, Keller-Schoenwetter S, Kunzi-Rapp K, Munstedt K, Rao
CV, Lang U, Preissner KT: Characterization of
human chorionic gonadotropin as a novel angiogenic
factor. J Clin Endocrinol Metab 87: 5290-6, 2002
|
klaus.t.preissner(at)biochemie.med.uni-giessen.de