Integrins as antimetastatic targets of RGD-independent snake venom components in liver metastasis [corrected]
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Integrins as antimetastatic targets of RGD-independent snake venom components in liver metastasis [corrected]. / Rosenow, Felix; Ossig, Rainer; Thormeyer, Dorit; Gasmann, Peter; Schlüter, Kerstin; Brunner, Georg; Haier, Jörg; Eble, Johannes A.
In: NEOPLASIA, Vol. 10, No. 2, 02.2008, p. 168-76.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Integrins as antimetastatic targets of RGD-independent snake venom components in liver metastasis [corrected]
AU - Rosenow, Felix
AU - Ossig, Rainer
AU - Thormeyer, Dorit
AU - Gasmann, Peter
AU - Schlüter, Kerstin
AU - Brunner, Georg
AU - Haier, Jörg
AU - Eble, Johannes A
PY - 2008/2
Y1 - 2008/2
N2 - 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 alpha2beta1 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 alpha2beta1 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.
AB - 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 alpha2beta1 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 alpha2beta1 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.
KW - Animals
KW - Antineoplastic Agents
KW - Carcinoma, Hepatocellular
KW - Cell Adhesion
KW - Cell Line, Tumor
KW - Cell Movement
KW - Collagen
KW - Colorectal Neoplasms
KW - Crotalid Venoms
KW - Fibronectins
KW - Humans
KW - Integrins
KW - Laminin
KW - Liver
KW - Liver Neoplasms
KW - Male
KW - Rats
KW - Rats, Sprague-Dawley
KW - Viper Venoms
M3 - SCORING: Journal article
C2 - 18283339
VL - 10
SP - 168
EP - 176
JO - NEOPLASIA
JF - NEOPLASIA
SN - 1476-5586
IS - 2
ER -