Antimetastatic Integrin as Inhibitors of Snake Venoms
Metastasis comprises several subsequent steps including local invasion and intravasation at the primary site, then their adhesion/arrest within the vessels of host organs followed by their extravasation and infiltration into the target organ stroma. In contrast to previous studies which have used a...
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Series: | Neoplasia: An International Journal for Oncology Research |
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doaj-726cd983f56c41659b34c78c8630801d2020-11-24T22:16:34ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-02-0110216817610.1593/neo.07898Antimetastatic Integrin as Inhibitors of Snake VenomsFelix Rosenow0Rainer Ossig1Dorit Thormeyer2Peter Gasmann3Kerstin Schlüter4Georg Brunner5Jörg Haier6Johannes A. Eble7Department of General Surgery, Muenster University Hospital, 48149 Muenster, GermanyInstitute for Physiological Chemistry, Muenster University Hospital, 48149 Muenster, GermanyDepartment of Cancer Research, Fachklinik Hornheide, University of Muenster, 48149 Muenster, GermanyDepartment of General Surgery, Muenster University Hospital, 48149 Muenster, GermanyDepartment of General Surgery, Muenster University Hospital, 48149 Muenster, GermanyDepartment of Cancer Research, Fachklinik Hornheide, University of Muenster, 48149 Muenster, GermanyDepartment of General Surgery, Muenster University Hospital, 48149 Muenster, GermanyInstitute for Physiological Chemistry, Muenster University Hospital, 48149 Muenster, Germany Metastasis comprises several subsequent steps including local invasion and intravasation at the primary site, then their adhesion/arrest within the vessels of host organs followed by their extravasation and infiltration into the target organ stroma. In contrast to previous studies which have used aspartate-glycine-arginine (RGD) peptides and antibodies against integrins, we used rare collagen- and laminin-antagonizing integrin inhibitors from snake venoms to analyze the colonization of the liver by tumor cells both by intravital microscopy and in vitro. Adhesion of liver-targeting tumor cells to the sinusoid wall components, laminin-1 and fibronectin, is essential for liver metastasis. This step is inhibited by lebein-1, but not by lebein-2 or rhodocetin. Both lebeins from the Vipera lebetina venom block integrin interactions with laminins in an RGD-independent manner. Rhodocetin is an antagonist of α2β1 integrin, a collagen receptor on many tumor cells. Subsequent to tumor cell arrest, extravasation into the liver stroma and micrometastasis are efficiently delayed by rhodocetin. This underlines the importance of α2β1 integrin interaction with the reticular collagen I-rich fibers in liver stroma. Antagonists of laminin- and collagen-binding integrins could be valuable tools to individually block the direct interactions of tumor cells with distinct matrix components of the Disse space, thereby reducing liver metastasis. http://www.sciencedirect.com/science/article/pii/S1476558608800632 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Felix Rosenow Rainer Ossig Dorit Thormeyer Peter Gasmann Kerstin Schlüter Georg Brunner Jörg Haier Johannes A. Eble |
spellingShingle |
Felix Rosenow Rainer Ossig Dorit Thormeyer Peter Gasmann Kerstin Schlüter Georg Brunner Jörg Haier Johannes A. Eble Antimetastatic Integrin as Inhibitors of Snake Venoms Neoplasia: An International Journal for Oncology Research |
author_facet |
Felix Rosenow Rainer Ossig Dorit Thormeyer Peter Gasmann Kerstin Schlüter Georg Brunner Jörg Haier Johannes A. Eble |
author_sort |
Felix Rosenow |
title |
Antimetastatic Integrin as Inhibitors of Snake Venoms |
title_short |
Antimetastatic Integrin as Inhibitors of Snake Venoms |
title_full |
Antimetastatic Integrin as Inhibitors of Snake Venoms |
title_fullStr |
Antimetastatic Integrin as Inhibitors of Snake Venoms |
title_full_unstemmed |
Antimetastatic Integrin as Inhibitors of Snake Venoms |
title_sort |
antimetastatic integrin as inhibitors of snake venoms |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2008-02-01 |
description |
Metastasis comprises several subsequent steps including local invasion and intravasation at the primary site, then their adhesion/arrest within the vessels of host organs followed by their extravasation and infiltration into the target organ stroma. In contrast to previous studies which have used aspartate-glycine-arginine (RGD) peptides and antibodies against integrins, we used rare collagen- and laminin-antagonizing integrin inhibitors from snake venoms to analyze the colonization of the liver by tumor cells both by intravital microscopy and in vitro. Adhesion of liver-targeting tumor cells to the sinusoid wall components, laminin-1 and fibronectin, is essential for liver metastasis. This step is inhibited by lebein-1, but not by lebein-2 or rhodocetin. Both lebeins from the Vipera lebetina venom block integrin interactions with laminins in an RGD-independent manner. Rhodocetin is an antagonist of α2β1 integrin, a collagen receptor on many tumor cells. Subsequent to tumor cell arrest, extravasation into the liver stroma and micrometastasis are efficiently delayed by rhodocetin. This underlines the importance of α2β1 integrin interaction with the reticular collagen I-rich fibers in liver stroma. Antagonists of laminin- and collagen-binding integrins could be valuable tools to individually block the direct interactions of tumor cells with distinct matrix components of the Disse space, thereby reducing liver metastasis.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558608800632 |
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