NGR (Asn-Gly-Arg)-targeted delivery of coagulase to tumor vasculature arrests cancer cell growth
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F18%3A43897508" target="_blank" >RIV/60076658:12310/18:43897508 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/18:00493248
Result on the web
<a href="https://www.nature.com/articles/s41388-018-0213-4" target="_blank" >https://www.nature.com/articles/s41388-018-0213-4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41388-018-0213-4" target="_blank" >10.1038/s41388-018-0213-4</a>
Alternative languages
Result language
angličtina
Original language name
NGR (Asn-Gly-Arg)-targeted delivery of coagulase to tumor vasculature arrests cancer cell growth
Original language description
Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Here we took advantage of the unique coagulation properties of staphylocoagulase and genetically engineered it to generate a new fusion protein with novel anti-cancer properties. This novel bi-functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA) motif that recognizes CD13 and alpha(v)beta(3) integrin receptors, targeting it to tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to an NGR sequence retained its normal binding activity with prothrombin and alpha(v)beta(3) integrins, as confirmed in silico and in vitro. Moreover, in vivo biodistribution studies demonstrated selective accumulation of FITC-labeled tCoa-NGR fusion proteins at the site of subcutaneously implanted PC3 tumor xenografts in nude mice. Notably, systemic administration of tCoa-NGR to mice bearing 4T1 mouse mammary xenografts or PC3 human prostate tumors resulted in a significant reduction in tumor growth. These anti-tumor effects were accompanied by massive thrombotic occlusion of small and large tumor vessels, tumor infarction and tumor cell death. From these findings, we propose tCoa-NGR mediated tumor infarction as a novel and promising anti-cancer strategy targeting both CD13 and integrin alpha(v)beta(3) positive tumor neovasculature.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Oncogene
ISSN
0950-9232
e-ISSN
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Volume of the periodical
37
Issue of the periodical within the volume
29
Country of publishing house
GB - UNITED KINGDOM
Number of pages
14
Pages from-to
3967-3980
UT code for WoS article
000439101300005
EID of the result in the Scopus database
2-s2.0-85045458141