RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F17%3A43895782" target="_blank" >RIV/60076658:12310/17:43895782 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/17:00477852

Result on the web

<a href="https://www.nature.com/articles/s41598-017-05326-9" target="_blank" >https://www.nature.com/articles/s41598-017-05326-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-017-05326-9" target="_blank" >10.1038/s41598-017-05326-9</a>

Result language

angličtina

Original language name

RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice

Original language description

Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and alpha(v)beta(3) endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments. Although free coagulase elicited robust coagulase activity in vitro, only targeted coagulase (tCoa-RGD) was capable of producing extensive thrombosis, and subsequent infarction and massive necrosis of CT26 mouse colon, 4T1 mouse mammary and SKOV3 human ovarian tumors in mice. Additionally, systemic injections of lower doses of tCoa-RGD produced striking tumor growth inhibition of CT26, 4T1 and SKOV3 solid tumors in animals. Altogether, the nontoxic nature, unique shortcut mechanism, minimal effective dose, wide therapeutic window, efficient induction of thrombosis, local effects and susceptibility of human blood to coagulase suggest tCoa-RGD fusion proteins as a novel and promising anticancer therapy for human trials.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

AUG 15 2017

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

—

UT code for WoS article

000407570000003

EID of the result in the Scopus database

—