Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype.
aging
breast cancer
epithelial-mesenchymal transition
extracellular matrix
lysyl oxidase
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
26
07
2021
received:
13
01
2021
pubmed:
8
10
2021
medline:
8
3
2022
entrez:
7
10
2021
Statut:
ppublish
Résumé
Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive normal human mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. Decellularized breast matrix from aged mice leads to loss of E-cadherin membrane localization in KTB21 cells, increased cell motility and invasion, and increased production of inflammatory cytokines and cancer-related proteins. The aged matrix upregulates cancer-related genes in KTB21 cells and enriches a cell subpopulation highly expressing epithelial-mesenchymal transition-related genes. Lysyl oxidase knockdown reverts the aged matrix-induced changes to the young levels; it relocalizes E-cadherin to cell membrane, and reduces cell motility, invasion, and cytokine production. These results show for the first time that the aging ECM harbors key biochemical, physical, and mechanical cues contributing to invasive and cancer-like behavior in healthy and cancer mammary cells. Differential response of cells to young and aged ECMs can lead to identification of new targets for cancer treatment and prevention.
Identifiants
pubmed: 34617419
doi: 10.1002/advs.202100128
pmc: PMC8596116
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2100128Subventions
Organisme : NIBIB NIH HHS
ID : R01 EB027660
Pays : United States
Organisme : NIH HHS
ID : F32 CA210583-01
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA236979
Pays : United States
Organisme : Walther Cancer Foundation
ID : 0184.01
Organisme : NIH HHS
ID : U01 CA236979
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA210583
Pays : United States
Organisme : NIH HHS
ID : 5R01EB027660-02
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA109545
Pays : United States
Informations de copyright
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
Références
Cancer Genomics Proteomics. 2014 Jul-Aug;11(4):175-94
pubmed: 25048347
Sci Rep. 2019 Oct 17;9(1):14933
pubmed: 31624357
Virchows Arch. 2019 Jan;474(1):3-12
pubmed: 30368555
Nat Methods. 2017 Sep;14(9):865-868
pubmed: 28759029
Elife. 2014 Mar 11;3:e01308
pubmed: 24618895
Sci Transl Med. 2018 Jan 3;10(422):
pubmed: 29298864
Biomark Res. 2019 Sep 11;7:20
pubmed: 31528346
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
Neoplasia. 2021 Mar;23(3):326-336
pubmed: 33621853
Biomaterials. 2018 Jul;170:37-48
pubmed: 29653286
Mol Oncol. 2014 May;8(3):483-507
pubmed: 24457100
Semin Cancer Biol. 2015 Dec;35:3-10
pubmed: 26416466
Front Cell Dev Biol. 2019 Jul 05;7:86
pubmed: 31334229
PLoS One. 2013 Aug 22;8(8):e72250
pubmed: 23991074
J Med Chem. 2019 Jun 27;62(12):5863-5884
pubmed: 31070916
Oncologist. 2014 Oct;19(10):1076-83
pubmed: 25142841
Sci Rep. 2017 Feb 10;7:42088
pubmed: 28186196
Acta Biomater. 2021 Mar 1;122:220-235
pubmed: 33359292
Crit Rev Oncol Hematol. 2008 Apr;66(1):65-74
pubmed: 17949989
Breast Cancer Res. 2018 Jun 14;20(1):55
pubmed: 29898756
Acta Biomater. 2014 Jan;10(1):194-204
pubmed: 24012606
Biosci Rep. 2017 Feb 23;37(1):
pubmed: 28096317
J Biomed Mater Res A. 2007 Dec 1;83(3):887-94
pubmed: 17567861
Mol Cancer Res. 2019 Jan;17(1):321-331
pubmed: 30224545
PLoS One. 2015 Dec 28;10(12):e0145813
pubmed: 26710072
Neoplasia. 2017 Aug;19(8):649-658
pubmed: 28732212
Bioessays. 2012 Jan;34(1):40-9
pubmed: 22086861
Int J Biol Macromol. 2019 Mar 1;124:444-450
pubmed: 30465840
Cell Rep. 2020 Dec 29;33(13):108566
pubmed: 33378681
Oncotarget. 2017 Dec 31;9(5):5545-5561
pubmed: 29464017
BMC Cancer. 2021 Feb 10;21(1):149
pubmed: 33568081
Neoplasia. 2011 May;13(5):406-18
pubmed: 21532881
Cancer Res. 1994 Jul 15;54(14):3668-71
pubmed: 8033081
J Biol Chem. 2010 Feb 26;285(9):6658-69
pubmed: 20026874
Eur J Dermatol. 2016 Aug 1;26(4):350-60
pubmed: 27124123
Nat Mater. 2020 Jul;19(7):797-806
pubmed: 32066931
Clin Cancer Res. 2004 Nov 15;10(22):7621-8
pubmed: 15569994
Int J Biol Macromol. 2019 Feb 1;122:1152-1162
pubmed: 30218727
Cell. 2020 Feb 6;180(3):585-600.e19
pubmed: 32004457
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6836-6841
pubmed: 30890638
J Natl Cancer Inst. 2001 Nov 7;93(21):1638-43
pubmed: 11698568
Mol Cell Biol. 2011 Aug;31(16):3286-97
pubmed: 21690299
Oncol Rep. 2021 Jun;45(6):
pubmed: 33846813
Blood. 2003 Apr 1;101(7):2762-9
pubmed: 12433678
J Cell Biol. 2007 Jul 30;178(3):425-36
pubmed: 17664334
AJR Am J Roentgenol. 2012 Mar;198(3):W292-5
pubmed: 22358028
Cancer Res. 2018 Sep 1;78(17):5107-5123
pubmed: 29997232
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4725-30
pubmed: 25825750
Biochem Biophys Res Commun. 2014 Feb 14;444(3):427-32
pubmed: 24472554
Oncol Rep. 2013 Dec;30(6):2725-32
pubmed: 24064911
Am J Pathol. 2010 Oct;177(4):1765-78
pubmed: 20813961
Cell Physiol Biochem. 2017;41(5):1851-1864
pubmed: 28376477
Sci Rep. 2016 Oct 20;6:35391
pubmed: 27762282
Curr Biol. 2019 Feb 18;29(4):578-591.e5
pubmed: 30744966
Cancers (Basel). 2018 Jul 10;10(7):
pubmed: 29996539
Int J Cancer. 1997 Jul 3;72(1):1-22
pubmed: 9212216
Biomech Model Mechanobiol. 2012 Nov;11(8):1241-9
pubmed: 22161021
Breast Cancer Res. 2000;2(2):116-24
pubmed: 11250701
Nat Cell Biol. 2008 Sep;10(9):1027-38
pubmed: 19160483
Biores Open Access. 2017 Jun 01;6(1):74-84
pubmed: 28736690
Oncogene. 2006 Apr 13;25(16):2379-92
pubmed: 16369494
Adv Sci (Weinh). 2021 Nov;8(22):e2100128
pubmed: 34617419
Biomed Mater. 2018 Feb 28;13(3):035005
pubmed: 29334080
Nat Rev Cancer. 2020 Feb;20(2):89-106
pubmed: 31836838
Nat Rev Cancer. 2001 Oct;1(1):46-54
pubmed: 11900251
Adv Drug Deliv Rev. 2014 Dec 15;79-80:214-21
pubmed: 24816064
Integr Biol (Camb). 2009 Jan;1(1):70-9
pubmed: 20023793
Anticancer Res. 2014 May;34(5):2173-83
pubmed: 24778019
Acta Biomater. 2020 Apr 1;106:1-21
pubmed: 32045679
Int J Cancer. 2010 Dec 15;127(12):2739-48
pubmed: 21351253
Front Cell Dev Biol. 2018 Apr 17;6:41
pubmed: 29719832
J Immunol. 2010 Jul 1;185(1):642-52
pubmed: 20530259
Oncotarget. 2015 Oct 6;6(30):29016-33
pubmed: 26359694
J Res Med Sci. 2013 Dec;18(12):1021-5
pubmed: 24523791
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Dec;161(4):339-347
pubmed: 29097819
Aging Dis. 2017 Oct 1;8(5):628-642
pubmed: 28966806
J Biol Chem. 2004 Dec 17;279(51):53331-7
pubmed: 15383546
Biomaterials. 2021 Jan;268:120554
pubmed: 33296796
Onco Targets Ther. 2016 Apr 13;9:2169-79
pubmed: 27110132
Cancer Discov. 2019 Jan;9(1):64-81
pubmed: 30279173
J Urol. 2005 Jan;173(1):10-20
pubmed: 15592017