Organoid-Transplant Model Systems to Study the Effects of Obesity on the Pancreatic Carcinogenesis
adipokines
carcinogenesis
obesity
organoid models
pancreatic cancer
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
12
2019
accepted:
07
04
2020
entrez:
16
5
2020
pubmed:
16
5
2020
medline:
16
5
2020
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality among adults in developed countries. The discovery of the most common genetic alterations as well as the development of organoid models of pancreatic cancer have provided insight into the fundamental pathways driving tumor progression from a normal cell to non-invasive precursor lesion and finally to widely metastatic disease, offering new opportunities for identifying the key driver of cancer evolution. Obesity is one of the most serious public health challenges of the 21st century. Several epidemiological studies have shown the positive association between obesity and cancer-related morbidity/mortality, as well as poorer prognosis and treatment outcome. Despite strong evidence indicates a link between obesity and cancer incidence, the molecular basis of the initiating events remains largely elusive. This is mainly due to the lack of an accurate and reliable model of pancreatic carcinogenesis that mimics human obesity-associated PDAC, making data interpretation difficult and often confusing. Here we propose a feasible and manageable organoid-based preclinical tool to study the effects of obesity on pancreatic carcinogenesis. Therefore, we tracked the effects of obesity on the natural evolution of PDAC in a genetically defined transplantable model of the syngeneic murine pancreatic preneoplastic lesion (mP) and tumor (mT) derived-organoids that recapitulates the progression of human disease from early preinvasive lesions to metastatic disease. Our results suggest that organoid-derived transplant in obese mice represents a suitable system to study early steps of pancreatic carcinogenesis and supports the hypothesis that inflammation induced by obesity stimulates tumor progression and metastatization during pancreatic carcinogenesis.
Identifiants
pubmed: 32411709
doi: 10.3389/fcell.2020.00308
pmc: PMC7198708
doi:
Types de publication
Journal Article
Langues
eng
Pagination
308Informations de copyright
Copyright © 2020 Lupo, Piro, Torroni, Delfino, Trovato, Rusev, Fiore, Filippini, De Sanctis, Manfredi, Marengo, Lawlor, Martini, Tortora, Ugel, Corbo, Melisi and Carbone.
Références
Pathol Int. 2000 Apr;50(4):263-72
pubmed: 10849311
World J Gastrointest Oncol. 2014 Sep 15;6(9):311-24
pubmed: 25232456
Nature. 2015 Feb 26;518(7540):495-501
pubmed: 25719666
Am J Surg Pathol. 2015 Dec;39(12):1730-41
pubmed: 26559377
Braz J Med Biol Res. 2013 Sep;46(9):758-64
pubmed: 24068191
Cancer Cell. 2003 Dec;4(6):437-50
pubmed: 14706336
J Biotechnol. 2010 Jul 1;148(1):16-23
pubmed: 20083148
Nat Rev Gastroenterol Hepatol. 2019 Apr;16(4):207-220
pubmed: 30718832
Pancreas. 2018 Sep;47(8):937-945
pubmed: 30113428
Int J Mol Sci. 2018 Oct 25;19(11):
pubmed: 30366466
Nat Rev Gastroenterol Hepatol. 2016 Dec 22;14(1):7-8
pubmed: 28003666
Sci Rep. 2019 Aug 22;9(1):12286
pubmed: 31439856
PPAR Res. 2008;2008:326915
pubmed: 18615182
Cancer Cell. 2014 May 12;25(5):621-37
pubmed: 24823639
Horm Mol Biol Clin Investig. 2015 Aug;23(2):39-46
pubmed: 26136304
Lancet Oncol. 2002 Sep;3(9):565-74
pubmed: 12217794
Surgery. 2009 Aug;146(2):258-63
pubmed: 19628082
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Exp Med. 2017 Mar 6;214(3):579-596
pubmed: 28232471
Cancer Cell. 2005 May;7(5):469-83
pubmed: 15894267
Iran J Cancer Prev. 2013 Fall;6(4):186-94
pubmed: 25250133
Nat Med. 2011 Oct 30;17(11):1498-503
pubmed: 22037646
Pancreas. 2018 May/Jun;47(5):516-525
pubmed: 29702529
Nature. 2017 Nov 23;551(7681):512-516
pubmed: 29132146
Am J Epidemiol. 2015 Aug 1;182(3):187-97
pubmed: 26085045
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
Nature. 2016 Mar 3;531(7592):47-52
pubmed: 26909576
J Immunol. 1998 Oct 15;161(8):4138-45
pubmed: 9780186
Nature. 2012 Apr 29;486(7402):266-70
pubmed: 22699621
Hematol Oncol Clin North Am. 2015 Aug;29(4):609-17
pubmed: 26226900
Cancer Discov. 2016 Aug;6(8):852-69
pubmed: 27246539
Obes Surg. 2011 Nov;21(11):1792-7
pubmed: 21842287
FEBS Lett. 2010 Aug 4;584(15):3242-9
pubmed: 20542036
Cell. 2015 Jan 15;160(1-2):324-38
pubmed: 25557080
J Am Coll Surg. 2009 May;208(5):989-94; discussion 994-6
pubmed: 19476877
Int J Cancer. 2007 May 1;120(9):1993-8
pubmed: 17266034
Biochem Biophys Rep. 2016 Sep;7:144-149
pubmed: 27617308
Cancer Prev Res (Phila). 2013 Oct;6(10):1064-73
pubmed: 23943783
Nat Genet. 2015 Oct;47(10):1168-78
pubmed: 26343385
BJU Int. 2003 May;91(7):716-20
pubmed: 12699491
Cell Metab. 2016 Jan 12;23(1):48-62
pubmed: 26771116
Physiol Behav. 2004 Apr;81(2):243-8
pubmed: 15159170
EMBO J. 2013 Oct 16;32(20):2708-21
pubmed: 24045232
Cancer Res. 2011 Apr 1;71(7):2455-65
pubmed: 21459803
Front Genet. 2013 Dec 17;4:288
pubmed: 24381581
Gastroenterology. 2019 Nov;157(5):1413-1428.e11
pubmed: 31352001
Cancer Prev Res (Phila). 2017 Sep;10(9):494-506
pubmed: 28864539
Int J Mol Sci. 2019 Sep 09;20(18):
pubmed: 31505876
Cell Rep. 2018 Apr 24;23(4):974-982
pubmed: 29694905
Cell Death Dis. 2015 Dec 31;6:e2037
pubmed: 26720346
J Clin Oncol. 2013 Nov 20;31(33):4229-34
pubmed: 24145341
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Trends Endocrinol Metab. 2017 Jan;28(1):46-62
pubmed: 27633129
Int J Obes (Lond). 2018 Mar;42(3):334-343
pubmed: 29151594
Methods Mol Biol. 2012;821:421-33
pubmed: 22125082
Cell. 2012 Jan 20;148(1-2):349-61
pubmed: 22265420
Gastroenterology. 2019 May;156(7):2085-2096
pubmed: 30721663
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Gut. 2012 Oct;61(10):1454-64
pubmed: 22234980
Int J Cancer. 2019 Apr 15;144(8):1877-1887
pubmed: 30259989
HPB (Oxford). 2006;8(5):324-36
pubmed: 18333084
Cancer Res. 2016 Dec 15;76(24):7160-7167
pubmed: 27780823
Clin Cancer Res. 2015 Aug 1;21(15):3522-8
pubmed: 25700304
Am J Clin Pathol. 2008 Sep;130(3):382-8
pubmed: 18701411
Br J Cancer. 2012 Feb 28;106(5):1004-10
pubmed: 22315049
Cancer Res. 2018 Feb 15;78(4):909-921
pubmed: 29269518
Cancer Res. 2009 Jun 15;69(12):5259-66
pubmed: 19491274