Endogenous Extracellular Matrix Regulates the Response of Osteosarcoma 3D Spheroids to Doxorubicin.
3D models
collagen
drug screening
extracellular matrix
osteosarcoma
spheroids
tumor microenvironment
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
14 Feb 2023
14 Feb 2023
Historique:
received:
20
01
2023
revised:
07
02
2023
accepted:
09
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
26
2
2023
Statut:
epublish
Résumé
The extracellular matrix (ECM) modulates cell behavior, shape, and viability as well as mechanical properties. In recent years, ECM disregulation and aberrant remodeling has gained considerable attention in cancer targeting and prevention since it may stimulate tumorigenesis and metastasis. Here, we developed an in vitro model that aims at mimicking the in vivo tumor microenvironment by recapitulating the interactions between osteosarcoma (OS) cells and ECM with respect to cancer progression. We long-term cultured 3D OS spheroids made of metastatic or non-metastatic OS cells mixed with mesenchymal stromal cells (MSCs); confirmed the deposition of ECM proteins such as Type I collagen, Type III collagen, and fibronectin by the stromal component at the interface between tumor cells and MSCs; and found that ECM secretion is inhibited by a neutralizing anti-IL-6 antibody, suggesting a new role of this cytokine in OS ECM deposition. Most importantly, we showed that the cytotoxic effect of doxorubicin is reduced by the presence of Type I collagen. We thus conclude that ECM protein deposition is crucial for modelling and studying drug response. Our results also suggest that targeting ECM proteins might improve the outcome of a subset of chemoresistant tumors.
Identifiants
pubmed: 36831562
pii: cancers15041221
doi: 10.3390/cancers15041221
pmc: PMC9954237
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : AIRC
ID : 21403
Organisme : Ministry of Health - 5 x 1000
ID : Anno 5X1000 2019
Organisme : National Recovery and Resilience Plan, PNRR_CN3
ID : CE_00000041
Références
Cancer Res. 2005 Mar 1;65(5):1748-54
pubmed: 15753370
Cancer Sci. 2017 Oct;108(10):1939-1946
pubmed: 28756624
Clin Exp Metastasis. 2019 Jun;36(3):171-198
pubmed: 30972526
Mol Cell Biochem. 2012 Oct;369(1-2):205-16
pubmed: 22782528
Cancer Cell Int. 2022 Apr 29;22(1):166
pubmed: 35488263
J Pathol. 2008 Feb;214(3):357-67
pubmed: 18044827
Toxicon. 2005 Sep 15;46(4):387-93
pubmed: 16051297
Cancer Treat Res. 2009;152:239-62
pubmed: 20213394
Methods Mol Biol. 2018;1686:201-213
pubmed: 29030823
Clin Cancer Res. 2015 Aug 1;21(15):3561-8
pubmed: 25695692
PLoS One. 2016 Nov 16;11(11):e0166500
pubmed: 27851822
Oncotarget. 2014 Sep 15;5(17):7575-88
pubmed: 25277190
Oncotarget. 2015 Oct 6;6(30):28988-98
pubmed: 26418748
Int J Mol Med. 1999 Jul;4(1):67-71
pubmed: 10373640
Cancers (Basel). 2021 Jan 15;13(2):
pubmed: 33467731
J Vet Intern Med. 2000 Sep-Oct;14(5):495-8
pubmed: 11012111
FEBS J. 2009 Sep;276(18):5275-86
pubmed: 19682073
N Engl J Med. 1995 Nov 23;333(21):1380-5
pubmed: 7477118
Cancer Lett. 2017 Oct 1;405:90-99
pubmed: 28774797
Front Mol Biosci. 2020 Jan 31;6:160
pubmed: 32118030
Mol Cancer. 2022 Apr 23;21(1):104
pubmed: 35461253
Int J Nanomedicine. 2018 Oct 04;13:6049-6058
pubmed: 30323592
Adv Anat Pathol. 2019 Jan;26(1):69-74
pubmed: 30339548
Ann Biomed Eng. 2014 Feb;42(2):352-67
pubmed: 24297495
Med Sci Monit. 2018 Dec 06;24:8812-8821
pubmed: 30518744
Int J Oncol. 2016 Jul;49(1):189-96
pubmed: 27176642
BMC Med. 2006 Dec 26;4(1):38
pubmed: 17190588
Cancer Res. 2018 Feb 15;78(4):950-961
pubmed: 29259017
J Cell Physiol. 2019 May;234(5):6927-6939
pubmed: 30204936
Cancer Cell. 2014 Nov 10;26(5):605-22
pubmed: 25517747
Curr Med Sci. 2022 Oct;42(5):1055-1065
pubmed: 36260267
Int J Cancer. 2017 Mar 15;140(6):1331-1345
pubmed: 27888521
Nat Med. 1997 Apr;3(4):378-80
pubmed: 9095165
J Biomech. 2022 Aug;141:111229
pubmed: 35933917
Rep Prog Phys. 2019 Jun;82(6):064602
pubmed: 30947151
Nat Metab. 2022 Jun;4(6):693-710
pubmed: 35760868
Oncogene. 2022 Jul;41(29):3705-3718
pubmed: 35732800
J Exp Clin Cancer Res. 2020 Sep 4;39(1):178
pubmed: 32887645
Curr Opin Cell Biol. 2010 Oct;22(5):697-706
pubmed: 20822891
Front Oncol. 2021 Aug 27;11:719922
pubmed: 34513697
Oncotarget. 2016 Aug 23;7(34):55141-55154
pubmed: 27409827
Front Oncol. 2020 Aug 18;10:1488
pubmed: 33014790
Soft Matter. 2007 Feb 14;3(3):299-306
pubmed: 32900146
Clin Orthop Relat Res. 1991 Sep;(270):159-68
pubmed: 1884536
Nat Commun. 2020 Oct 9;11(1):5120
pubmed: 33037194
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Apr 28;43(4):368-382
pubmed: 29774872
Cells. 2020 Mar 06;9(3):
pubmed: 32155954
Int J Mol Sci. 2018 Sep 20;19(10):
pubmed: 30241395
Pathol Res Pract. 2022 Nov;239:154179
pubmed: 36274380
Oncotarget. 2016 Sep 27;7(39):63408-63423
pubmed: 27566564
ILAR J. 2014;55(1):69-85
pubmed: 24936031
World J Surg Oncol. 2019 Jan 28;17(1):23
pubmed: 30691475
Cancers (Basel). 2021 Nov 22;13(22):
pubmed: 34831016
Cancer Lett. 2012 Dec 1;325(1):80-8
pubmed: 22743617
Clin Cosmet Investig Dermatol. 2014 Nov 06;7:301-11
pubmed: 25395868
J Clin Invest. 2017 Oct 2;127(10):3770-3783
pubmed: 28891814
Front Physiol. 2019 Jun 26;10:814
pubmed: 31316395
Cancer Res. 2011 Feb 1;71(3):634-9
pubmed: 21266356
Front Oncol. 2020 Apr 15;10:397
pubmed: 32351878
Semin Cancer Biol. 2022 Nov;86(Pt 3):224-236
pubmed: 35331851
Stem Cell Res Ther. 2018 Jan 31;9(1):22
pubmed: 29386041
Clin Cancer Res. 2017 Jul 15;23(14):3721-3733
pubmed: 28053020