Novel multivalent S100A8 inhibitory peptides attenuate tumor progression and metastasis by inhibiting the TLR4-dependent pathway.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
16
08
2022
accepted:
23
02
2023
revised:
20
01
2023
medline:
21
7
2023
pubmed:
19
3
2023
entrez:
18
3
2023
Statut:
ppublish
Résumé
The tumor-elicited inflammation is closely related to tumor microenvironment during tumor progression. S100A8, an endogenous ligand of Toll-like receptor 4 (TLR4), is known as a key molecule in the tumor microenvironment and premetastatic niche formation. We firstly generated a novel multivalent S100A8 competitive inhibitory peptide (divalent peptide3A5) against TLR4/MD-2, using the alanine scanning. Divalent peptide3A5 suppressed S100A8-mediated interleukin-8 and vascular endothelial growth factor production in human colorectal tumor SW480 cells. Using SW480-transplanted xenograft models, divalent peptide3A5 suppressed tumor progression in a dose-dependent manner. We demonstrated that combination therapy with divalent peptide3A5 and bevacizumab synergistically suppressed tumor growth in SW480 xenograft models. Using syngeneic mouse models, we found that divalent peptide3A5 improved the efficacy of anti-programmed death (PD)1 antibody, and lung metastasis. In addition, by using multivalent peptide library screening based on peptide3A5, we then isolated two more candidates; divalent ILVIK, and tetravalent ILVIK. Of note, multivalent ILVIK, but not monovalent ILVIK showed competitive inhibitory activity against TLR4/MD-2 complex, and anti-tumoral activity in SW480 xenograft models. As most tumor cells including SW480 cells also express TLR4, S100A8 inhibitory peptides would target both the tumor microenvironment and tumor cells. Thus, multivalent S100A8 inhibitory peptides would provide new pharmaceutical options for aggressive cancers.
Identifiants
pubmed: 36932197
doi: 10.1038/s41417-023-00604-3
pii: 10.1038/s41417-023-00604-3
pmc: PMC10021052
doi:
Substances chimiques
Calgranulin B
0
Toll-Like Receptor 4
0
Vascular Endothelial Growth Factor A
0
Calgranulin A
0
Peptides
0
TLR4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
973-984Informations de copyright
© 2023. The Author(s).
Références
Oncogene. 2011 Aug 4;30(31):3429-39
pubmed: 21399660
Mol Pharmacol. 2006 Apr;69(4):1288-95
pubmed: 16373689
Cancer Res. 2011 Mar 1;71(5):1989-98
pubmed: 21363926
Am J Pathol. 2013 Jan;182(1):192-205
pubmed: 23141927
Cell. 2007 Sep 7;130(5):906-17
pubmed: 17803912
Cancer Res. 2019 Sep 15;79(18):4715-4728
pubmed: 31337655
Nat Med. 2005 Nov;11(11):1173-9
pubmed: 16244651
J Exp Med. 2008 Sep 29;205(10):2235-49
pubmed: 18809714
Nat Immunol. 2010 May;11(5):373-84
pubmed: 20404851
Cancer Metastasis Rev. 1989 Aug;8(2):98-101
pubmed: 2673568
Proc Natl Acad Sci U S A. 2012 May 8;109(19):7421-6
pubmed: 22532668
Nature. 2005 Dec 8;438(7069):820-7
pubmed: 16341007
Int J Oncol. 2020 Jan;56(1):101-112
pubmed: 31746424
Nat Med. 2007 Nov;13(11):1324-32
pubmed: 17952090
J Biol Chem. 2001 Aug 17;276(33):31332-9
pubmed: 11402040
J Biol Chem. 2001 Mar 30;276(13):10229-33
pubmed: 11150311
Sci Signal. 2011 Nov 15;4(199):ra75
pubmed: 22087031
J Immunol. 2013 Aug 15;191(4):1856-64
pubmed: 23858030
J Immunol. 2004 Nov 1;173(9):5398-405
pubmed: 15494486
Nature. 2009 Apr 30;458(7242):1191-5
pubmed: 19252480
Appl Environ Microbiol. 2015 Feb;81(3):1092-100
pubmed: 25452283
J Immunol. 2001 Sep 1;167(5):2887-94
pubmed: 11509636
Nat Med. 2012 Aug;18(8):1279-85
pubmed: 22842477
Front Oncol. 2018 Nov 05;8:496
pubmed: 30456203
J Leukoc Biol. 2001 Jul;70(1):59-64
pubmed: 11435486
J Immunol. 2002 May 15;168(10):5233-9
pubmed: 11994480
Nat Rev Immunol. 2021 Aug;21(8):485-498
pubmed: 33526920
Oncogene. 2016 Mar 17;35(11):1445-56
pubmed: 26165843
J Immunother Cancer. 2019 Dec 5;7(1):343
pubmed: 31806053
Science. 2004 Feb 6;303(5659):848-51
pubmed: 14764882
Science. 2002 Nov 1;298(5595):1025-9
pubmed: 12411706
FASEB J. 2006 Dec;20(14):2597-9
pubmed: 17065223
Nat Med. 2014 Jun;20(6):676-81
pubmed: 24859530
Nat Med. 2007 Sep;13(9):1042-9
pubmed: 17767165
Cell. 2020 Sep 17;182(6):1401-1418.e18
pubmed: 32810439
J Clin Invest. 2005 Aug;115(8):2223-33
pubmed: 16025156
Leukemia. 2011 Jan;25(1):57-65
pubmed: 21072048
J Immunol. 2020 May 1;204(9):2589-2599
pubmed: 32198140
Nat Cell Biol. 2006 Dec;8(12):1369-75
pubmed: 17128264
Nat Cell Biol. 2008 Nov;10(11):1349-55
pubmed: 18820689
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11942-7
pubmed: 20547845
J Biol Chem. 2002 Apr 26;277(17):15028-34
pubmed: 11836257