Senescent mesenchymal stem cells remodel extracellular matrix driving breast cancer cells to a more-invasive phenotype.
Breast cancer
Cancer cell invasion
Cell motility
ECM remodeling
Mesenchymal stem cells
Senescence
Tumor microenvironment
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
23 01 2020
23 01 2020
Historique:
received:
27
03
2019
accepted:
19
12
2019
pubmed:
15
1
2020
medline:
15
4
2021
entrez:
15
1
2020
Statut:
epublish
Résumé
Mesenchymal stem cells (MSCs) are essential for the regenerative process; however, biological aging and environmental stress can induce senescence - an irreversible state of growth arrest - that not only affects the behavior of cells but also disrupts their ability to restore tissue integrity. While abnormal tissue properties, including increased extracellular matrix stiffness, are linked with the risk of developing breast cancer, the role and contribution of senescent MSCs to the disease progression to malignancy are not well understood. Here, we investigated senescence-associated biophysical changes in MSCs and how this influences cancer cell behavior in a 3D matrix interface model. Although senescent MSCs were far less motile than pre-senescent MSCs, they induced an invasive breast cancer phenotype, characterized by increased spheroid growth and cell invasion in collagen gels. Further analysis of collagen gels using second-harmonic generation showed increased collagen density when senescent MSCs were present, suggesting that senescent MSCs actively remodel the surrounding matrix. This study provides direct evidence of the pro-malignant effects of senescent MSCs in tumors.
Identifiants
pubmed: 31932504
pii: jcs.232470
doi: 10.1242/jcs.232470
pmc: PMC6983709
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL134625
Pays : United States
Informations de copyright
© 2020. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
Références
Annu Rev Biomed Eng. 2015;17:113-141
pubmed: 26643020
Semin Cell Dev Biol. 2009 Oct;20(8):931-41
pubmed: 19682592
Cancer Res. 2008 Jun 1;68(11):4331-9
pubmed: 18519693
Int J Mol Sci. 2016 Jul 19;17(7):
pubmed: 27447618
Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494
pubmed: 29762782
Cell. 2009 Nov 25;139(5):891-906
pubmed: 19931152
Trends Genet. 2016 Nov;32(11):751-761
pubmed: 27692431
Cancer Cell. 2011 Jun 14;19(6):695-7
pubmed: 21665143
Breast Cancer Res. 2015 Mar 20;17:42
pubmed: 25887413
J Cell Sci. 2005 Feb 1;118(Pt 3):485-96
pubmed: 15657080
J Clin Invest. 2011 Aug;121(8):3206-19
pubmed: 21737876
J Cell Biol. 2011 Feb 21;192(4):547-56
pubmed: 21321098
Sci Rep. 2018 May 8;8(1):7248
pubmed: 29739990
Front Genet. 2017 Dec 19;8:220
pubmed: 29312442
Biochim Biophys Acta. 2014 Aug;1840(8):2386-95
pubmed: 24721714
J Invest Dermatol. 2016 Jan;136(1):74-83
pubmed: 26763426
Mol Biol Cell. 2005 Jan;16(1):328-38
pubmed: 15483053
Cell. 2005 May 6;121(3):335-48
pubmed: 15882617
FASEB J. 2014 Sep;28(9):3906-18
pubmed: 24858279
Stem Cells. 2009 Jun;27(6):1288-97
pubmed: 19492299
Biol Res. 2016 Jul 28;49(1):34
pubmed: 27464526
Cell Commun Signal. 2017 May 4;15(1):17
pubmed: 28472950
F1000Res. 2016 Sep 07;5:null
pubmed: 27635242
Nat Cell Biol. 2007 Dec;9(12):1392-400
pubmed: 18037882
J Phys D Appl Phys. 2017 Oct 27;50(48):483001
pubmed: 29628530
Nat Rev Cancer. 2006 May;6(5):392-401
pubmed: 16572188
PLoS One. 2009 Jun 09;4(6):e5846
pubmed: 19513108
Sci Rep. 2017 Feb 10;7:42088
pubmed: 28186196
Mol Aspects Med. 2018 Apr;60:92-103
pubmed: 29146100
Stem Cells. 2013 Jan;31(1):146-55
pubmed: 23034897
Cancer Res. 2007 Apr 1;67(7):3117-26
pubmed: 17409418
PLoS One. 2016 Nov 3;11(11):e0166027
pubmed: 27812189
Sci Rep. 2018 Aug 9;8(1):11935
pubmed: 30093656
Sci Rep. 2015 Nov 20;5:16941
pubmed: 26585689
Stem Cell Res Ther. 2018 Sep 26;9(1):257
pubmed: 30257725
Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12072-7
pubmed: 11593017
Exp Cell Res. 2013 Mar 10;319(5):684-96
pubmed: 23228958
J Cell Biol. 2014 Mar 3;204(5):669-82
pubmed: 24567359
Nat Rev Mol Cell Biol. 2009 Jan;10(1):75-82
pubmed: 19197334
Nat Cell Biol. 2013 Jun;15(6):637-46
pubmed: 23708000
Nature. 2007 Oct 4;449(7162):557-63
pubmed: 17914389
J Cell Biol. 2003 Jan 20;160(2):267-77
pubmed: 12527751
Cancer Res. 2002 Jul 1;62(13):3603-8
pubmed: 12097260
Int J Oncol. 2017 Oct;51(4):1300-1310
pubmed: 28902360
Stem Cells Dev. 2014 Feb 1;23(3):245-61
pubmed: 24093435
Nucleus. 2015;6(4):254-60
pubmed: 26107557
Oncotarget. 2015 Oct 13;6(31):31164-80
pubmed: 26378036
Nat Rev Cancer. 2001 Dec;1(3):203-13
pubmed: 11902575
Stem Cells. 2012 Dec;30(12):2810-9
pubmed: 23034983
Oncol Lett. 2017 Sep;14(3):2611-2620
pubmed: 28927027
ACS Chem Biol. 2015 Aug 21;10(8):1932-8
pubmed: 26046821
Aging Cell. 2017 Jun;16(3):518-528
pubmed: 28371268
Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):E6447-E6456
pubmed: 27698134
Mol Biol Cell. 2017 Jul 7;28(14):1984-1996
pubmed: 28057760
J Biomed Opt. 2014 Jan;19(1):16007
pubmed: 24407500
Nat Methods. 2009 Feb;6(2):143-5
pubmed: 19151720
Cancer Lett. 2015 Jun 1;361(2):155-63
pubmed: 25700776
Annu Rev Physiol. 2013;75:685-705
pubmed: 23140366
Oncol Rep. 2016 Nov;36(5):2745-2754
pubmed: 27633896
Science. 2013 Aug 30;341(6149):1240104
pubmed: 23990565
J Cell Biol. 2018 Oct 1;217(10):3330-3342
pubmed: 30194270
J Proteome Res. 2008 Apr;7(4):1470-80
pubmed: 18271524
PLoS One. 2012;7(3):e33248
pubmed: 22438903
Oncotarget. 2015 Apr 10;6(10):8155-66
pubmed: 25544750
Cancer Res. 2008 Oct 1;68(19):7864-71
pubmed: 18829542
J Cell Sci. 2010 Dec 15;123(Pt 24):4195-200
pubmed: 21123617
Cancer Cell. 2005 Sep;8(3):241-54
pubmed: 16169468
FASEB J. 2015 Apr;29(4):1280-9
pubmed: 25491311
Lab Invest. 2008 Feb;88(2):196-206
pubmed: 18059364
Biophys J. 2002 Dec;83(6):3162-76
pubmed: 12496086
Oncotarget. 2015 Oct 13;6(31):30516-31
pubmed: 26483365
Oncotarget. 2016 Sep 13;7(37):60752-60774
pubmed: 27542276
Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10271-10276
pubmed: 16801550
Exp Gerontol. 2005 Dec;40(12):926-30
pubmed: 16125890
Cell Death Dis. 2013 Nov 07;4:e911
pubmed: 24201810
J Cell Biochem. 2006 Aug 1;98(5):1076-84
pubmed: 16619257
Annu Rev Biochem. 2015;84:131-64
pubmed: 25747401
Nat Rev Immunol. 2008 Sep;8(9):726-36
pubmed: 19172693
Nat Rev Mol Cell Biol. 2014 Jul;15(7):482-96
pubmed: 24954210
PLoS One. 2017 Nov 21;12(11):e0187635
pubmed: 29161296
Science. 2012 Oct 12;338(6104):212-5
pubmed: 23066072
Nat Cell Biol. 2013 Aug;15(8):978-90
pubmed: 23770676
Nat Commun. 2017 Jan 27;8:14056
pubmed: 28128198
Curr Opin Cell Biol. 2011 Feb;23(1):55-64
pubmed: 21109415