Inflammation Associated Pancreatic Tumorigenesis: Upregulation of Succinate Dehydrogenase (Subunit B) Reduces Cell Growth of Pancreatic Ductal Epithelial Cells.
SDHB
chronic pancreatitis
inflammatory stroma
macrophages
pancreatic cancer
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
21 Dec 2019
21 Dec 2019
Historique:
received:
16
11
2019
revised:
12
12
2019
accepted:
19
12
2019
entrez:
28
12
2019
pubmed:
28
12
2019
medline:
28
12
2019
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is amongst the most fatal malignancies and its development is highly associated with inflammatory processes such as chronic pancreatitis (CP). Since the succinate dehydrogenase subunit B (SDHB) is regarded as tumor suppressor that is lost during cancer development, this study investigated the impact of M1-macrophages as part of the inflammatory microenvironment on the expression as well as function of SDHB in benign and premalignant pancreatic ductal epithelial cells (PDECs). Immunohistochemical analyses on pancreatic tissue sections from CP patients and control individuals revealed a stronger SDHB expression in ducts of CP tissues being associated with a greater abundance of macrophages compared to ducts in control tissues. Accordingly, indirect co-culture with M1-macrophages led to clearly elevated SDHB expression and SDH activity in benign H6c7-pBp and premalignant H6c7-kras PDECs. While siRNA-mediated SDHB knockdown in these cells did not affect glucose and lactate uptake after co-culture, SDHB knockdown significantly promoted PDEC growth which was associated with increased proliferation and decreased effector caspase activity particularly in co-cultured PDECs. Overall, these data indicate that SDHB expression and SDH activity are increased in PDECs when exposed to pro-inflammatory macrophages as a counterregulatory mechanism to prevent excessive PDEC growth triggered by the inflammatory environment.
Identifiants
pubmed: 31877753
pii: cancers12010042
doi: 10.3390/cancers12010042
pmc: PMC7016879
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SCHA-677/15-1
Organisme : UKSH Förderstiftung
ID : not applicable
Déclaration de conflit d'intérêts
The Authors declare no conflict of interest.
Références
Mediators Inflamm. 2015;2015:816460
pubmed: 26089604
Cancer Res. 2015 Apr 15;75(8):1567-79
pubmed: 25878146
Oncotarget. 2017 May 25;8(34):57813-57825
pubmed: 28915713
Biochem J. 2012 Apr 15;443(2):573-84
pubmed: 22280412
Cancer Res. 2005 Jun 15;65(12):5045-53
pubmed: 15958547
Cancer Metab. 2014 Dec 15;2:21
pubmed: 25671108
Cell Cycle. 2012 Aug 15;11(16):3019-35
pubmed: 22874531
Science. 2009 May 22;324(5930):1029-33
pubmed: 19460998
Pathologe. 2005 Feb;26(1):12-7
pubmed: 15630571
Immunobiology. 1995 Jul;193(2-4):193-203
pubmed: 8530143
Arch Biochem Biophys. 2014 Mar 1;545:69-73
pubmed: 24393743
Cell Cycle. 2013 May 1;12(9):1371-84
pubmed: 23574725
Cell Cycle. 2011 Jun 1;10(11):1772-83
pubmed: 21558814
Gastroenterology. 2005 May;128(6):1606-25
pubmed: 15887154
Langenbecks Arch Surg. 2008 Jul;393(4):535-45
pubmed: 18193270
Am J Surg Pathol. 2014 Apr;38(4):560-6
pubmed: 24625421
Cancer Cell. 2005 Jan;7(1):77-85
pubmed: 15652751
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
World J Gastroenterol. 2014 Aug 28;20(32):11182-98
pubmed: 25170203
FASEB J. 2012 Nov;26(11):4506-16
pubmed: 22835832
Cancer Res. 1982 May;42(5):1809-16
pubmed: 6802484
Am J Pathol. 1998 Jul;153(1):263-9
pubmed: 9665487
Oncogene. 2007 Apr 26;26(19):2759-68
pubmed: 17086212
Cancer Lett. 2015 Apr 10;359(2):165-8
pubmed: 25617800
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19402-7
pubmed: 24218566
Oncotarget. 2015 May 30;6(15):13371-86
pubmed: 25945836
Nat Rev Cancer. 2005 Nov;5(11):857-66
pubmed: 16327764
Oncogene. 2018 Jan 4;37(1):39-51
pubmed: 28846107
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
Mol Cell Biol. 2008 Jan;28(2):718-31
pubmed: 17967865
Biochim Biophys Acta. 2011 Nov;1807(11):1432-43
pubmed: 21771581
Nat Rev Cancer. 2016 Oct;16(10):635-49
pubmed: 27634447
Exp Ther Med. 2018 Jan;15(1):864-872
pubmed: 29399091
Int J Cancer. 2014 Aug 15;135(4):843-61
pubmed: 24458546
World J Gastroenterol. 2016 Mar 7;22(9):2678-700
pubmed: 26973408
Best Pract Res Clin Gastroenterol. 2010 Jun;24(3):349-58
pubmed: 20510834
Surg Oncol. 2002 May;10(4):153-69
pubmed: 12020670
Oncogene. 2006 Aug 7;25(34):4675-82
pubmed: 16892081
Cancer Lett. 2019 Jul 1;453:95-106
pubmed: 30930235
Trends Immunol. 2002 Nov;23(11):549-55
pubmed: 12401408
Cell Cycle. 2009 Dec;8(23):3984-4001
pubmed: 19923890
Biochim Biophys Acta. 2013 May;1827(5):565-72
pubmed: 23000077
Genes Dev. 2006 May 15;20(10):1218-49
pubmed: 16702400
PLoS One. 2014 May 05;9(5):e94357
pubmed: 24797069
Nat Rev Cancer. 2003 Nov;3(11):859-68
pubmed: 14668816
Cancer Cell. 2014 Jul 14;26(1):121-135
pubmed: 25002027
Lancet. 2001 Feb 17;357(9255):539-45
pubmed: 11229684
Int J Cancer. 2007 Aug 15;121(4):699-705
pubmed: 17534898
Am J Pathol. 1996 Jun;148(6):1763-70
pubmed: 8669463
Immunity. 2014 Jul 17;41(1):14-20
pubmed: 25035950
Oncotarget. 2015 Jul 10;6(19):16832-47
pubmed: 26164081
Mol Biol Cell. 2009 Apr;20(8):2174-85
pubmed: 19261809
Cancer Lett. 2014 Apr 10;345(2):203-9
pubmed: 23981573
J Ovarian Res. 2014 Dec 10;7:115
pubmed: 25491408
Science. 2003 Jan 31;299(5607):700-4
pubmed: 12560550
Nature. 2006 May 25;441(7092):431-6
pubmed: 16724054
Nat Rev Cancer. 2011 May;11(5):325-37
pubmed: 21508971
Free Radic Biol Med. 2017 Nov;112:149-161
pubmed: 28739529
J Immunol Methods. 2012 Jan 31;375(1-2):196-206
pubmed: 22075274
Oncol Res Treat. 2015;38(3):117-22
pubmed: 25792083
Science. 1956 Feb 24;123(3191):309-14
pubmed: 13298683