Peptide-2 from mouse myostatin precursor protein alleviates muscle wasting in cancer-associated cachexia.
Animals
Bone Morphogenetic Proteins
/ metabolism
Cachexia
/ drug therapy
Carcinoma, Lewis Lung
/ complications
Growth Differentiation Factors
/ metabolism
Hep G2 Cells
Humans
Male
Mice
Muscle, Skeletal
/ drug effects
Myostatin
/ antagonists & inhibitors
Neoplasms
/ complications
Peptides
/ genetics
Protein Precursors
/ genetics
Signal Transduction
/ drug effects
Lewis lung carcinoma
cancer cachexia
mice model
muscle wasting
myostatin
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
04
02
2020
revised:
01
06
2020
accepted:
01
06
2020
pubmed:
11
6
2020
medline:
15
12
2020
entrez:
11
6
2020
Statut:
ppublish
Résumé
Cancer cachexia, characterized by continuous muscle wasting, is a key determinant of cancer-related death; however, there are few medical treatments to combat it. Myostatin (MSTN)/growth differentiation factor 8 (GDF-8), which is a member of the transforming growth factor-β family, is secreted in an inactivated form noncovalently bound to the prodomain, negatively regulating the skeletal muscle mass. Therefore, inhibition of MSTN signaling is expected to serve as a therapeutic target for intractable muscle wasting diseases. Here, we evaluated the inhibitory effect of peptide-2, an inhibitory core of mouse MSTN prodomain, on MSTN signaling. Peptide-2 selectively suppressed the MSTN signal, although it had no effect on the activin signal. In contrast, peptide-2 slightly inhibited the GDF-11 signaling pathway, which is strongly related to the MSTN signaling pathway. Furthermore, we found that the i.m. injection of peptide-2 to tumor-implanted C57BL/6 mice alleviated muscle wasting in cancer cachexia. Although peptide-2 was unable to improve the loss of heart weight and fat mass when cancer cachexia model mice were injected with it, peptide-2 increased the gastrocnemius muscle weight and muscle cross-sectional area resulted in the enhanced grip strength in cancer cachexia mice. Consequently, the model mice treated with peptide-2 could survive longer than those that did not undergo this treatment. Our results suggest that peptide-2 might be a novel therapeutic candidate to suppress muscle wasting in cancer cachexia.
Identifiants
pubmed: 32519375
doi: 10.1111/cas.14520
pmc: PMC7419029
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
Gdf11 protein, mouse
0
Growth Differentiation Factors
0
Mstn protein, mouse
0
Myostatin
0
Peptides
0
Protein Precursors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2954-2964Subventions
Organisme : Japan Society for the Promotion of Science
Organisme : MEXT-Supported Program for the Strategic Research Foundation at Private Universities
ID : 2015-2019
Organisme : Japanese Ministry of Education, Culture, Sports, Science, and Technology
ID : 17K08794
Informations de copyright
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Lancet Oncol. 2011 May;12(5):489-95
pubmed: 21296615
J Med Invest. 2007 Aug;54(3-4):276-88
pubmed: 17878677
Expert Opin Drug Discov. 2009 Nov 1;4(11):1145-1155
pubmed: 20160874
Mol Cancer Ther. 2015 Jul;14(7):1661-70
pubmed: 25908685
Curr Opin Clin Nutr Metab Care. 2008 Jul;11(4):400-7
pubmed: 18541999
World J Surg. 2012 Jul;36(7):1509-16
pubmed: 22526034
Science. 2002 May 24;296(5572):1486-8
pubmed: 12029139
Skelet Muscle. 2016 Jul 26;6:26
pubmed: 27462398
PLoS One. 2015 Jul 30;10(7):e0133713
pubmed: 26226340
Biochem Biophys Res Commun. 2003 Jan 24;300(4):965-71
pubmed: 12559968
Circ Res. 2016 Apr 1;118(7):1125-41; discussion 1142
pubmed: 27034275
Skelet Muscle. 2018 Oct 27;8(1):34
pubmed: 30368252
J Med Chem. 2015 Feb 12;58(3):1544-9
pubmed: 25569186
Cancer Sci. 2020 Aug;111(8):2954-2964
pubmed: 32519375
N Engl J Med. 2004 Jun 24;350(26):2682-8
pubmed: 15215484
Front Physiol. 2019 Feb 18;10:41
pubmed: 30833900
Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R716-26
pubmed: 21677277
Nature. 1997 May 1;387(6628):83-90
pubmed: 9139826
Nat Genet. 1997 Sep;17(1):71-4
pubmed: 9288100
Eur J Cancer. 2006 Jan;42(1):31-41
pubmed: 16314085
J Biol Chem. 1998 Aug 14;273(33):21145-52
pubmed: 9694870
JCSM Clin Rep. 2018 Jul-Dec;3(2):
pubmed: 31134216
Blood. 2012 May 31;119(22):5320-8
pubmed: 22498737
Int J Biochem Cell Biol. 2013 Oct;45(10):2333-47
pubmed: 23721881
Biochem Biophys Rep. 2016 Apr 20;6:209-219
pubmed: 28955879
Physiol Rep. 2014 Mar 20;2(3):e00262
pubmed: 24760516
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9306-11
pubmed: 11459935
Clin Nutr. 2008 Dec;27(6):793-9
pubmed: 18718696
EMBO J. 1998 Jun 1;17(11):3091-100
pubmed: 9606191
Clin Genet. 2000 Jan;57(1):16-25
pubmed: 10733231
Neuromuscul Disord. 2007 Apr;17(4):290-6
pubmed: 17336525
Cell. 2010 Aug 20;142(4):531-43
pubmed: 20723755
Mol Pharmacol. 2002 Jul;62(1):65-74
pubmed: 12065756
J Cachexia Sarcopenia Muscle. 2018 Oct;9(5):871-879
pubmed: 30051975
Clin Cases Miner Bone Metab. 2014 Sep;11(3):215-21
pubmed: 25568656
J Phys Ther Sci. 2015 Jul;27(7):2349-52
pubmed: 26311981
PLoS Genet. 2007 May 25;3(5):e79
pubmed: 17530926
Bio Protoc. 2017 Apr 20;7(8):
pubmed: 28713848
Nat Commun. 2017 Apr 28;8:15153
pubmed: 28452368
Nat Rev Clin Oncol. 2013 Feb;10(2):90-9
pubmed: 23207794
Cold Spring Harb Perspect Biol. 2016 May 02;8(5):
pubmed: 27141051
Mol Pharmacol. 2002 Jul;62(1):58-64
pubmed: 12065755
Mol Ther. 2011 Jan;19(1):204-10
pubmed: 20700111