Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM).
angiogenesis
angiopoietin
co-option
colorectal cancer liver metastases
histopathological growth patterns
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
20 Dec 2019
20 Dec 2019
Historique:
received:
17
10
2019
revised:
12
12
2019
accepted:
19
12
2019
entrez:
28
12
2019
pubmed:
28
12
2019
medline:
28
12
2019
Statut:
epublish
Résumé
Colorectal cancer liver metastases (CRCLM) that receive their blood supply via vessel co-option are associated with a poor response to anti-angiogenic therapy. Angiopoietins (Ang1 and Ang2) with their Tyrosine-protein kinase receptor (Tie2) have been shown to support vessel co-option. We demonstrate significantly higher expression of Ang1 in hepatocytes adjacent to the tumor region of human chemonaïve and treated co-opting (replacement histopathological growth patterns: RHGP) tumors. To investigate the role of the host Ang1 expression, Ang1 knockout (KO) mice were injected intra-splenically with metastatic MC-38 colon cancer cells that develop co-opting liver metastases. We observed a reduction in the number of liver metastases and interestingly, for the first time, the development of angiogenic driven desmoplastic (DHGP) liver metastases. In addition, in-vitro, knockout of Ang1 in primary hepatocytes inhibited viability, migration and invasion ability of MC-38 cells. We also demonstrate that Ang 1 alone promotes the migration and growth of both human and mouse colon cancer cell lines These results provide evidence that high expression of Ang1 in the host liver is important to support vessel co-option (RHGP lesions) and when inhibited, favours the formation of angiogenic driven liver metastases (DHGP lesions).
Identifiants
pubmed: 31877668
pii: cancers12010035
doi: 10.3390/cancers12010035
pmc: PMC7016878
pii:
doi:
Types de publication
Journal Article
Langues
eng
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11205-10
pubmed: 12163646
Dig Surg. 2003;20(6):481-96
pubmed: 13679642
J Clin Oncol. 2012 Feb 1;30(4):441-4
pubmed: 22184396
Cancer Res. 2015 Dec 15;75(24):5235-47
pubmed: 26483205
Int J Cancer. 2001 Oct 1;94(1):6-15
pubmed: 11668472
Angiogenesis. 2018 Nov;21(4):849-860
pubmed: 29959560
Circ Res. 2000 Sep 29;87(7):603-7
pubmed: 11009566
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20730-5
pubmed: 22143796
Nat Med. 2016 Nov;22(11):1294-1302
pubmed: 27748747
Chin J Cancer. 2016 Jan 08;35:10
pubmed: 26747273
Int J Oncol. 2009 Jan;34(1):79-87
pubmed: 19082480
Cell. 2010 Mar 19;140(6):883-99
pubmed: 20303878
Ann N Y Acad Sci. 2015 Jul;1347:45-51
pubmed: 25773744
Cancer Cell. 2004 Dec;6(6):553-63
pubmed: 15607960
Br J Cancer. 2017 Nov 7;117(10):1427-1441
pubmed: 28982110
Int J Dev Biol. 2011;55(3):261-8
pubmed: 21710434
Physiol Rev. 2011 Jul;91(3):1071-121
pubmed: 21742796
J Biol Chem. 2011 Feb 11;286(6):4257-63
pubmed: 21147780
Am J Pathol. 1993 Sep;143(3):926-36
pubmed: 7689793
J Clin Invest. 2011 Jun;121(6):2278-89
pubmed: 21606590
J Pathol Clin Res. 2018 Jul;4(3):184-192
pubmed: 29654716
CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30
pubmed: 26742998
Cancer Res. 2001 Feb 15;61(4):1255-9
pubmed: 11245414
Nat Rev Cancer. 2010 Aug;10(8):575-85
pubmed: 20651738
Int J Mol Sci. 2016 Sep 06;17(9):
pubmed: 27608016
Oncol Lett. 2018 Jan;15(1):1313-1318
pubmed: 29387247
J Pathol. 2001 Oct;195(3):336-42
pubmed: 11673831
Expert Rev Anticancer Ther. 2009 Dec;9(12):1829-47
pubmed: 19954294
Am J Pathol. 2004 Nov;165(5):1557-70
pubmed: 15509526