Open Access
Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth
Тип публикации: Journal Article
Дата публикации: 2013-10-10
scimago Q1
wos Q2
БС1
SJR: 0.803
CiteScore: 5.4
Impact factor: 2.6
ISSN: 19326203
PubMed ID:
24130833
Multidisciplinary
Краткое описание
BackgroundNew strategies for the treatment of hepatocellular carcinoma (HCC) are needed, given that currently available chemotherapeutics are inefficient. Since tumor growth reflects the net balance between pro-proliferative and death signaling, agents shifting the equilibrium toward the latter are of considerable interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively induce apoptosis in malignant cells. Fn14•TRAIL, a fusion protein bridging these two pathways, has the potential to inhibit tumor growth, by interfering with TWEAK:Fn14 signaling, while at the same time enforcing TRAIL:TRAIL-R-mediated apoptosis. Consequently, Fn14•TRAIL's capacity to inhibit HCC growth was tested. ResultsFn14•TRAIL induced robust apoptosis of multiple HCC cell lines, while sparing non-malignant hepatocyte cell lines. Differential susceptibility to this agent did not correlate with expression levels of TRAIL, TRAIL-R, TWEAK and Fn14 by these lines. Fn14•TRAIL was more potent than soluble TRAIL, soluble Fn14, or a combination of the two. The requirement of both of Fn14•TRAIL's molecular domains for function was established using blocking antibodies directed against each of them. Subcutaneous injection of Fn14•TRAIL abrogated HCC growth in a xenograft model, and was well tolerated by the mice. ConclusionsIn this study, Fn14•TRAIL, a multifunctional fusion protein originally designed to treat autoimmunity, was shown to inhibit the growth of HCC, both in vitro and in vivo. The demonstration of this fusion protein’s potent anti-tumor activity suggests that simultaneous targeting of two signaling axes by a single fusion can serve as a basis for highly effective anti-cancer therapies.
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ГОСТ
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Aronin A. et al. Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth // PLoS ONE. 2013. Vol. 8. No. 10. p. e77050.
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Aronin A., Amsili S., PRIGOZHINA T. B., Tzdaka K., RACHMILEWITZ J., Shani N., Tykocinski M. L., Dranitzki-Elhalel M. Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth // PLoS ONE. 2013. Vol. 8. No. 10. p. e77050.
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TY - JOUR
DO - 10.1371/journal.pone.0077050
UR - https://doi.org/10.1371/journal.pone.0077050
TI - Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth
T2 - PLoS ONE
AU - Aronin, Alexandra
AU - Amsili, Shira
AU - PRIGOZHINA, TATYANA B.
AU - Tzdaka, Kobi
AU - RACHMILEWITZ, Jacob
AU - Shani, Noam
AU - Tykocinski, Mark L.
AU - Dranitzki-Elhalel, Michal
PY - 2013
DA - 2013/10/10
PB - Public Library of Science (PLoS)
SP - e77050
IS - 10
VL - 8
PMID - 24130833
SN - 1932-6203
ER -
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@article{2013_Aronin,
author = {Alexandra Aronin and Shira Amsili and TATYANA B. PRIGOZHINA and Kobi Tzdaka and Jacob RACHMILEWITZ and Noam Shani and Mark L. Tykocinski and Michal Dranitzki-Elhalel},
title = {Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth},
journal = {PLoS ONE},
year = {2013},
volume = {8},
publisher = {Public Library of Science (PLoS)},
month = {oct},
url = {https://doi.org/10.1371/journal.pone.0077050},
number = {10},
pages = {e77050},
doi = {10.1371/journal.pone.0077050}
}
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MLA
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Aronin, Alexandra, et al. “Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth.” PLoS ONE, vol. 8, no. 10, Oct. 2013, p. e77050. https://doi.org/10.1371/journal.pone.0077050.